Minakem | Lubricants Glidants | Excipient by Application

Minafin Group appoints Olivier Ubrich as CEO of Health Chemistry Division

05 Sep 2024

// PRESS RELEASE

The EDQM has validated updated CEP of Vinorelbine of Minakem, sole Mfg in Europe

25 Jun 2024

// PRESS RELEASE

Minakem Canada is manufacturing steroid APIs in a brand-new production unit

17 May 2024

// PRESS RELEASE

DATA COMPILATION
#PharmaFlow

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CPhI Worldwide, Milan

Booth #5A73

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DIGITAL CONTENT

3 INTERVIEW #SpeakPharma, 1 VLOG #PharmaReel, 13 CORPORATE CONTENT #SupplierSpotlight, 3 COMPANY BIO #AboutSupplier, 2 DATA COMPILATION #PharmaFlow, 65 NEWS #PharmaBuzz

media
3 INTERVIEW #SpeakPharma
1 VLOG #PharmaReel
13 CORPORATE CONTENT #SupplierSpotlight
3 COMPANY BIO #AboutSupplier
2 DATA COMPILATION #PharmaFlow
65 NEWS #PharmaBuzz

ACTIVE PHARMA INGREDIENTS

73 All APIs, 21 USDMF, 10 CEP/COS, 4 JDMF, 13 KDMF, 27 NDC API, 1 VMF, 67 Listed APIs

73 All APIs
21 USDMF
10 CEP/COS
4 JDMF
13 KDMF
27 NDC API
1 VMF
67 Listed APIs

DEVELOPMENTS

2 Drugs in Development

2 Drugs in Development

INTERMEDIATES

49 ALL Intermediates

49 ALL Intermediates

KEY PRODUCTS

1,1-Cyclobutane Dicarboxylic Acid, Budesonide, Cyclobutane Carboxaldehyde, Cyclopropyl Methyl Bromide, Cyclopropyl Methyl Chloride, Esomeprazole Magnesium, Esomeprazole Sodium, Fulvestrant, Ibrutinib, Methyl (1R,2S,5S)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate HCl, Propyl Gallate, Remifentanil, Vinblastine Sulfate, Vincristine Sulfate, Vinorelbine Tartrate

1,1-Cyclobutane Dicarboxylic Acid
Budesonide
Cyclobutane Carboxaldehyde
Cyclopropyl Methyl Bromide
Cyclopropyl Methyl Chloride
Esomeprazole Magnesium
Esomeprazole Sodium
Fulvestrant
Ibrutinib
Methyl (1R,2S,5S)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate HCl
Propyl Gallate
Remifentanil
Vinblastine Sulfate
Vincristine Sulfate
Vinorelbine Tartrate

SERVICES

API Manufacturing, API & Drug Product Development

KEY SERVICES

Continuous Flow Chemistry, Synthesis of Advanced Intermediates, Polymorph, Salt & Cocrystal Study, API Custom Synthesis, CDMO for High Potency APIs (HPAPIs), HPAPI Contract Manufacturing

Continuous Flow Chemistry
Synthesis of Advanced Intermediates
Polymorph, Salt & Cocrystal Study
API Custom Synthesis
CDMO for High Potency APIs (HPAPIs)
HPAPI Contract Manufacturing

EXCIPIENTS

2 Listed Products

excipientPortfolio
2 Listed Products

KEY EXCIPIENTS

Propyl Gallate GMP

Propyl Gallate GMP

EXCIPIENTS BY INGREDIENTS

Sodium Stearyl Fumarate, Propyl Gallate

excipientsByIngredients
Sodium Stearyl Fumarate
Propyl Gallate

EXCIPIENTS BY APPLICATIONS

API Stability Enhancers, Lubricants & Glidants

excipientsByApplications
API Stability Enhancers
Lubricants & Glidants

INSPECTIONS & REGISTRATIONS

15 FDA, 26 EDQM, 2 GDUFA, 2 Others

inspections
15 FDA
26 EDQM
2 GDUFA
2 Others

Minakem offers CDMO services for API & HPAPI, generics, regulatory expertise, track record performance & FDA & GMP certifications.

About

Minakem is a fully integrated development partner and commercial manufacturer for pharma companies. With around 70 years of experience, Minakem is a technology-driven company with expertise in complex multi-step synthesis, pressure chemistry, chiral synthesis, halogenation chemistry, steroid chemistry and prazole chemistry. It offers custom development & manufacturing, API manufacturing and the production of key intermediates. Minakem has 3 USFDA-approved development and manufacturing sites in France and Belgium. Minakem is an affiliate of the Minafin Group and has access to all technologies, resources, and capabilities.

CPhI Worldwide, MilanCPhI Worldwide, Milan

Industry Trade Show

Booth #5A73

08-10 October, 2024

Fiera Milano, Italy
euroPLX 86 MunicheuroPLX 86 Munich

Industry Trade Show

Attending

18-19 November, 2024

Munich, Germany
BOS ManchesterBOS Manchester

Industry Trade Show

Exhibiting

26-27 November, 2024

Manchester, UK

CONTACT DETAILS

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Country

France

Address

224 Avenue de la Dordogne, 59640 Dunkerque

Telephone

+33 320646830

contact@minakem.com

Website

https://minakem.com/

https://www.linkedin.com/company/minakem

Digital content

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INTERVIEW #SpeakPharma

"Minafin appoints Sébastien Poncet, Managing Director of Minakem Generics & New Therapies"

Sébastien Poncet is charged with enhancing the portfolio of proprietary processes and seizing opportunities in new therapies. Louvain-la-Neuve, January 27, 2022 – The Health Chemistry division of the Minafin Group today welcomes Sébastien Poncet as managing director of the Minakem Generics and New Therapies business unit. He is also an executive member of the division. Sébastien is a graduate of the Montpellier School of Chemistry Engineering (ENSCM) and holds a master's degree in business: B2B strategy and marketing from EM Lyon and participated in several international management programs from IMD Lausanne and from INSEAD. Over the past 20 years, he has held numerous sales positions at Solvay, Clariant (now Curia), Johnson Matthey, and Minafin. Sébastien is returning to the Minafin Group following an eight-year tenure at Fareva, where for the last two years he was a member of the executive committee. Frédéric Gauchet, chairman of the Minafin Group, said: "Sébastien’s appointment reflects our desire to enhance our portfolio of proprietary processes for manufacturing generic active ingredients in support of the efforts authorities are taking to secure a European drug supply. Minafin has the advanced know-how in fine chemistry required to enable the development of innovative therapies. But in order to remain at the cutting-edge of ‘new technologies,’ we may consider potential acquisitions in high value-added chemistry or biotechnology." Sébastien will focus on developing the business of active pharmaceutical ingredients that are within the public domain and seizing commercial opportunities generated by emerging therapies such as Messenger RNAs. “I am very pleased to start working again with the world-class teams at Minakem. They are globally recognized for their capacity to design innovative chemical routes, to scale them up successfully and their proven track record agility in the field of active ingredients. And I look forward to collaborating with them on the generic API product portfolio that I see has significant growth potential,” said Sébastien “As for new therapies, the sanitary crisis we are going through has demonstrated their importance in the therapeutic arsenal against COVID-19, for example, messenger RNA vaccines. These new technologies developed with high value-added chemistry are where Minakem’s Research & Development know-how can really make a difference in the years to come.” About the Minafin Group Health Chemistry Division The Health Chemistry division develops and manufactures active ingredients for the pharmaceutical industry through its two business units: Minakem CDMO and Minakem Generics & New Therapies. Minakem is the leader in Europe. It offers a wide range of cutting-edge technologies and pharmaceutical services to ensure that its customers have a seamless supply of high-quality products. The company provides its expertise for the development of exclusive manufacturing processes and to produce active pharmaceutical ingredients following cGMP conditions. Patients' needs being at the heart of its activities, the Healthcare Chemistry division ensures that the drugs it manufactures meet the strictest health and environmental safety standards. Minakem CDMO focuses on proprietary custom synthesis while Minakem Generics & New Therapies develops proprietary manufacturing processes for generic active ingredients and innovative therapies. The three production sites of the Healthcare Chemistry division, approved by the FDA, are located in Louvain-la-Neuve (BE), Dunkirk (FR) and Beuvry-la-Forêt (FR). Created in 2004, Minafin's Health Chemistry division employs 550 people. www.minakem.com About the Minafin Group The Minafin Group is a leading process developer and manufacturer of fine chemicals with three main areas of expertise: health chemistry, green chemistry, and challenging chemistry. Minafin operates six industrial manufacturing sites across Europe and North America. They provide customers in pharmaceuticals, life-science ingredients and added-value chemicals for high-tech application, with a range of proprietary processes, custom manufacturing, R&D, analytical and regulatory services, as well as formulations. Minafin invests significantly in R&D to create value for customers by specializing in innovations and eco-friendly solutions that bring a competitive edge and sustainability. Its strong industrial capabilities are consolidated through nine business units: Minakem CDMO, Minakem Generics, Blendamix, Pennakem, Minasolve, Minagro, EcoXtract, Minascent and Pressure Chemicals, which generated over €243M (approx. $280M) in revenue in 2020. Founded in 2004 as a privately held industrial company, Minafin is headquartered in Belgium and employs 900+ staff. www.minafin.com Press contact: Sylvie Boone –Press Relations Minafin Group –Sylvie.boone@minafin.com –32/497.540.945

Impressions: 1395

VLOG #PharmaReel

Your Highly Reliable CDMO Partner

CORPORATE CONTENT #SupplierSpotlight

Product List 2024

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Corporate Presentation

GMP Certificate 2023

Building Blocks & GMP Excipients 2021

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CDMO for Custom APIs & HPAPIs

Analytical Services

A Word With Minakem Teknoscienze

Minakem Interview

Challenging Chemistry in Pharmaceutical Manufacturing

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Corporate Video

Plant Based Food Developing New Ingredients by EcoXtract

High Containment Lab

DATA COMPILATION #PharmaFlow

Excipient Market Overview: Roquette, Seqens, Evonik make strategic moves; new guidelines deal with contamination

The pharmaceutical industry has long recognized the critical role excipients or inactive ingredients play in drug formulation and delivery. Excipients can comprise up to 90 percent of a medicine's total ingredients and serve crucial functions as binders, disintegrants, coatings, preservatives, colors, and flavorings. According to recent market research, the pharmaceutical excipients market was valued at US$ 9.27 billion in 2023. It is growing at a compound annual growth rate (CAGR) of 7.03 percent and is projected to reach US$ 18.48 billion by 2032. The main factors driving market growth is an increased demand for multifunctional excipients, coupled with the expanding use of generic medications. The development in the biologics sector and advancements in nanotechnology are also contributing significantly to market growth. Major excipient providers include BASF, Evonik, Merck KGaA owned MilliporeSigma, Gangwal Healthcare, Roquette Frères, DuPont, Croda International, Seqens, Boai NKY Pharmaceuticals, PMC Isochem, Minakem, Kewpie Corporation, Ashland Global, SPI Pharma, Pfanstiehl, Nanjing Well Pharmaceutical, ICE Pharma, Anhui Ribobay Pharmaceutical and Nippon Fine Chemical. View Our Dashboard on Major Excipient Companies in 2024 (Free Excel Available) WHO, India’s CDSCO tighten regulations; new GMP guidelines implemented to curb contamination Last year, the World Health Organization (WHO) issued a health alert linking at least 300 child deaths in the Gambia, Uzbekistan, and Indonesia to the ingestion of contaminated cough syrups containing unacceptable levels of diethylene glycol (DEG) and ethylene glycol (EG). In response to the tragic events, the WHO released two draft appendices to its guideline on good manufacturing practices (GMPs) for excipients this year. Manufacturers are now required to use suitable risk assessment tools to identify and mitigate potential hazards. Since India-made cough syrups had been linked to the deaths, India’s drug regulator — Central Drugs Standard Control Organization (CDSCO) — took steps to prevent contamination, and advised drugmakers to only use pharmaceutical-grade excipients from approved sources. Furthermore, the Indian Health Ministry proposed amendments to the Drugs and Cosmetics Rules, 1945 to include details of excipients on drug labels. While listing all excipients on every strip of medicine may be challenging, the ministry suggested mentioning those causing hypersensitivity on the label. Applicants now mandatorily need to submit evidence of stability and safety of excipients. These regulatory developments have significant implications for excipient manufacturers and pharmaceutical companies worldwide. Leading pharmaceutical excipient firms like Gangwal Healthcare, Sigachi Industries, and Nitika Pharmaceuticals are well-positioned to meet these heightened quality and safety standards, given their long-standing commitment to producing high-quality, compliant excipients. View Our Dashboard on Major Excipient Companies in 2024 (Free Excel Available) Roquette buys IFF’s pharma unit for US$ 2.85 bn; Evonik opens new spray-drying facility in Darmstadt In a significant industry move, France-based Roquette entered into an agreement to acquire IFF's pharma solutions business in a deal valued at US$ 2.85 billion. This acquisition is set to rebalance family-owned Roquette’s portfolio around health and nutrition. The deal is expected to accelerate Roquette’s growth and significantly strengthen its presence in the excipients market. Evonik has opened a new facility for drying aqueous dispersions of its Eudragit polymers at its site in Darmstadt, Germany. The facility will help Evonik meet increasing demand from drugmakers for its oral drug delivery solutions. The plant uses green energy solutions. The company has also partnered University of Mainz to commercialize a new class of polyethylene glycols (PEG) lipids for nucleic acid delivery. Evonik’s Health Care business has been growing its nucleic acid drug and vaccine delivery portfolio. Germany’s Johannes Gutenberg University of Mainz was the first to develop randomized polyethylene glycols (rPEGs). This collaboration aims to expand Evonik’s toolbox of technologies for nucleic acid-based medicines, offering an improved immunogenicity profile for lipid nanoparticle carriers used in mRNA vaccines and therapeutics. Asahi Kasei made significant strides in addressing a pressing industry concern that emerged in 2018 when potentially carcinogenic nitrosamine impurities were detected in several pharmaceuticals. Guided by regional authorities, such as the European Medicines Agency and the US Food and Drug Administration, the pharmaceutical industry has been carrying out extensive assessments and research to identify the cause of these impurities. In response to this challenge, Asahi Kasei developed its Ceolus microcrystalline cellulose with extremely low nitrite levels. The Japanese company achieved nitrite concentrations of 0.1 micrograms per gram or less, which is equivalent to 0.1 parts per million (ppm). The company also started full commercial operation of its second manufacturing facility for Ceolus in Japan, enhancing supply capacity and stability. JRS Pharma and Gujarat Microwax opened a state-of-the-art cotton-based croscarmellose sodium plant in Mehsana, Gujarat (India). This facility aims to produce high-quality excipients that meet global standards, potentially reducing India's dependency on imports and boosting its presence in the global excipient market. The Indian excipient industry accounts for less than 1 percent of the global market share. View Our Dashboard on Major Excipient Companies in 2024 (Free Excel Available) Seqens to advance innovative polymer; biologics, personalized medicine create demand for specialized excipients Recent industry collaborations highlight the ongoing innovation in novel excipients. France’s Seqens, with over 20 years of polymer development experience, was chosen by Pleryon Therapeutics to advance its leading osteoarthritis candidate – an innovative GMP polymer. This collaboration leverages Seqens’ newly expanded and modernized cGMP plant in Aramon, France, demonstrating the industry’s commitment to investing in advanced manufacturing capabilities for novel excipients. The rise of biologics and personalized medicine has created a demand for specialized excipients capable of stabilizing complex molecules and enabling targeted drug delivery. Roquette’s launch of Lycagel Flex, a hydroxypropyl pemix for nutraceutical and pharmaceutical softgel capsules, exemplifies this trend. Built on Roquette’s market-first Lycagel pea starch technology, this plant-based alternative to gelatin offers manufacturers the flexibility to customize formulations for a range of production and end-user needs. The innovative pea starch foundation also underscores the industry’s move towards sustainable bio-based excipients. The trend towards patient-centric drug development has also influenced excipient innovation. Excipients that can improve palatability, ease of swallowing, or enable novel dosage forms (such as orally disintegrating tablets) are in high demand. For example, IFF brought a super disintegrant Ac-Di-Sol, that supports faster disintegration and drug dissolution in oral disintegrating tablets, improving patient experience. View Our Dashboard on Major Excipient Companies in 2024 (Free Excel Available) Our view The heightened regulatory scrutiny on excipients due to product contamination incidents has created a high risk perception and uncertainty around the regulatory acceptance of novel excipients. That said, novel excipients are central to the development of new drug modalities and therapies. Going forward, sustainability will also become an increasingly important factor in excipient selection and development. As the industry innovates towards biologics, personalized therapies, and patient-centric formulations, the role of high-quality, multifunctional excipients will only grow more vital in ensuring drug stability, bioavailability, and patient compliance. Companies that can navigate the complex regulatory landscape, invest in R&D, and offer high-quality, multifunctional excipients will be well-positioned to succeed in this evolving market.

Impressions: 766

CDMO Activity Tracker: Novo’s parent buys Catalent for US$ 16.5 bn; Fujifilm, Merck KGaA, Axplora expand capabilities

During the first half (H1) of 2024, the global contract development and manufacturing organization (CDMO) landscape was driven by the escalating demand for complex drug development and manufacturing.With the industry grappling with constantly evolving therapeutic modalities, CDMOs are racing to invest in cutting-edge technologies and infrastructure to meet the growing needs of pharmaceutical and biotech companies.Some of the key players in the CDMO space are Catalent, EUROAPI, Lonza, Axplora, Thermo Fisher, SEQENS, Samsung Biologics, Fujifilm Diosynth Biotechnologies, Quotient Sciences, Famar, LGM Pharma, Veranova, and Evonik.View CDMO Activity Tracker for H1 2024 (Free Excel Available) Novo’s parent buys Catalent for US$ 16.5 bn; Bora, Lonza, Siegfried expand US footprintDuring H1 2024, several European and Asian drugmakers expanded their footprints in the US. In February, Novo Nordisk’s parent company, the Novo Nordisk Foundation, announced the acquisition of Catalent through its investment arm Novo Holdings for US$ 16.5 billion. Novo Holdings plans to sell three of Catalent’s “fill-finish” sites to Novo Nordisk for US$ 11 billion. The deal is expected to allow the Danish drugmaker “to serve significantly more people living with diabetes and obesity,” a company statement said.Taiwan-headquartered Bora Pharmaceuticals forged ahead with its expansion plans in the US market by acquiring Minnesota-based generics manufacturer Upsher-Smith Laboratories. Emergent BioSolutions said it is selling its Maryland facility to an affiliate of Bora. This site in Camden is part of its CDMO, Emergent Bioservices, and offers clinical and commercial non-viral aseptic fill/finish services on four fill lines, including lyophilization, formulation development, and support services.Swiss drugmaker Lonza has agreed to acquire Genentech’s manufacturing facility in California, US, from Roche for US$ 1.2 billion in cash. The site, located in the city of Vacaville, is one of the largest biologics manufacturing facilities in the world by volume.Lonza also launched an artificial intelligence-driven route design technology for choosing the optimal synthetic pathway to manufacture novel APIs.Switzerland’s Siegfried is acquiring a Wisconsin (US)-based CDMO that specializes in early-phase development and manufacturing services from Curia Global to strengthen its capabilities in North America. Siegfried will further develop the site into its North American Siegfried Acceleration Hub for early-phase CDMO services.View CDMO Activity Tracker for H1 2024 (Free Excel Available) Merck Millipore, SK Bioscience lead CGT boom; Fujifilm, Axplora, expand CDMO capabilitiesThe burgeoning field of cell and gene therapies (CGTs) is driving significant investments in CDMOs. CGTs saw considerable deal-making too. Merck KGaA agreed to buy Wisconsin-based Mirus Bio for US$ 600 million. Mirus Bio is a specialist in the development and commercialization of transfection reagents that are used to help introduce genetic material into cells. These reagents play a key role in the production of viral vectors for CGTs.Similarly, South Korea’s SK Bioscience acquired a 60 percent stake in IDT Biologika GmbH for KRW 339 billion (US$ 244 million). IDT Biologika is a 104-year-old German company that ranks among the top 10 vaccine producers in the world.CDMOs are also expanding their capabilities in order to lead innovation for their pharmaceutical partners. Fujifilm Diosynth Biotechnologies is investing US$ 1.2 billion in its large-scale cell culture CDMO business to further expand its end-to-end bio-manufacturing facility in North Carolina, bringing the total investment in the facility to over US$ 3.2 billion. Similarly, Merck KGaA owned MilliporeSigma made its biggest investment in the Asia-Pacific region in March when it invested € 300 million (US$ 327 million) in a new bioprocessing production center in Daejeon, South Korea.German CDMO giant Axplora is investing € 8 million (US$ 8.73 million) to expand capacity for antibody drug conjugate (ADC) payload manufacturing at its Le Mans site in France. Catalent completed upgrades to its capsule filling capabilities of dry powders for inhalation to handle potent drugs at its Boston facility. This now positions Catalent as the CDMO with the largest GMP capacity for capsule spray-dried and carrier-based inhaled powders.LGM Pharma increased its Analytical Testing Services (ATS) by 50 percent with a US$ 2 million investment and introduced new suppository manufacturing capabilities to its CDMO portfolio. Minakem has invested in a new production unit in Montreal, Canada, for steroid APIs.View CDMO Activity Tracker for H1 2024 (Free Excel Available) EUROAPI kicks off four-year sweeping plan; LegoChem partners Samsung Biologics for ADC programSanofi’s spinoff EUROAPI marked 2024 as a “transition year”, setting in motion its Focus-27 plan for profitable growth in the future. The sweeping four-year plan includes a streamlined value-added portfolio focused on highly differentiated and profitable APIs, and a CDMO focused on late-stage and high-value complex small molecules and tides supported by unique technological platforms. The leading French small molecules player signed a five-year collaboration with Ireland’s Priothera wherein EUROAPI will develop and industrialize the manufacturing process of an innovative, complex molecule for blood cancers – mocravimod. The project will be carried out at EUROAPI’s site in Budapest, which is its center of excellence for complex chemistry.South Korea’s CDMO powerhouse Samsung Biologics has partnered LegoChem Biosciences and will provide antibody development and drug substance manufacturing services as a part of LegoChem’s ADC program designed to treat solid tumors. LegoChem aims to submit an investigational new drug application to the US Food and Drug Administration (FDA) in the first half of 2025. Aurigene and Vipergen have joined forces to offer DNA-encoded library (DEL) screening for drug discovery. By combining Aurigene’s drug discovery capabilities with Vipergen’s DEL screening technologies, they seek to create a powerful tool that can quickly test over a billion small-molecule compounds against different disease targets. Dr. Reddy’s Laboratories’ company Aurigene also inaugurated its biologics facility spread across 70,000 square feet.Chinese biotech startup Pleryon is collaborating with France’s SEQENS, a leader in specialty ingredients, to develop and manufacture the former’s lead candidate, an innovative polymer to treat osteoarthritis. Famar is collaborating with Lavipharm and will serve as the contract manufacturer for the latter’s recently added analgesic pharmaceutical products — Lonarid N and Lonalgal.View CDMO Activity Tracker for H1 2024 (Free Excel Available) Our view Key trends observed in H1 2024 include a surge in investments for fill-finish facilities, a growing emphasis on cell and gene therapies, and advancements in ADC manufacturing. With the proliferation of these new classes of drugs, the CDMO space has been rapidly changing in recent years. In the future, the integration of digital technologies, such as AI and automation, will be a key differentiator for CDMOs looking to optimize their operations and accelerate drug development timelines.

Impressions: 2458

COMPANY BIO #AboutSupplier

Looking for highly potent drug substances or HPAPIs? Find a CDMO, CMO offering high potent complex APIs, intermediates & cytotoxics on PharmaCompass.

Looking for highly potent drug substances or HPAPIs? Find a CDMO, CMO offering high potent complex APIs, intermediates & cytotoxics on PharmaCompass. Q1. What are High Potency APIs (HPAPIs)? How do HPAPIs differ from APIs? High Potency APIs (HPAPIs) are defined as Active Pharmaceutical Ingredients (APIs) that require special handling due to toxicity and use extremely small doses in finished drugs. High Potent Active Pharmaceutical Ingredients (HPAPI) are effective at much smaller dosage levels than traditional APIs, but their potent characteristics present specific highly potent API handling challenges. Although there is no standard classification for the potency of pharmaceuticals, all potent molecules can be defined as powerfully active, noxious materials needing only very small quantities of dosing to have an effect. HPAPI compounds or highly potent compounds are also known for their ability to target diseased cells more precisely and selectively than other APIs. Highly Potent Active Pharmaceutical Ingredients (HPAPIs) or High Potency Active Pharmaceutical Ingredients (HPAPIs) are extremely effective pharmacologically active ingredients. A growing number of pharmaceutical products contain Highly Potent Active Pharmaceutical Ingredients (HPAPIs), which has led to an explosive growth in demand for the production of HPAPIs using state of the art development methods of Highly Active Pharmaceutical Ingredients (HAPIs) whilst adhering to current Good Manufacturing Practice (cGMP) guidelines. These highly potent API or high-potency APIs (HPAPIs) are frequently characterized by complex API structures requiring multi-step processes or semi-synthesis, often involving more than 10 steps. For drug-substance manufacturing, the highly potent API (HPAPI) may be a small-molecule, biologic compound or antibody drug conjugate (ADC), which contains a cytotoxic compound, a small-molecule bound to a monoclonal antibody. High-Potency APIs (HPAPIs) are most commonly used in hormonal drugs for breast cancer, followed by glaucoma medication. Highly potent API services (High potent CDMO services) are also used in formulating cardiovascular drugs, central nervous system drugs and musculoskeletal drugs. Therefore, the high-potency API (HPAPI) market covers a wide range of product types across several therapeutic areas, although oncology-focused medicines continue to lead in terms of innovative pipeline candidates and upcoming generic entries. Q2. What are the special facilities required for the handling and development of HPAPIs? The cytotoxicity of High Potency Active Pharmaceutical Ingredients (HPAPIs) or Highly Active Pharmaceutical Ingredients (HAPIs) presents highly potent API handling challenges and requires heavy investment in specialized containment equipment to ensure that employees and their environment are protected from exposure. HPAPIs are complex APIs which require specialized facility design, equipment, operation and process safety throughout their drug development process and commercial scale production, in order to overcome HAPI containment challenges and ensure operator safety. Large-scale highly potent API (HPAPI) manufacturing, is therefore increasingly being outsourced to specialized contract development and manufacturing organizations (CDMOs) offering contract development and manufacturing of highly potent APIs with exceptional infrastructure, expertise and track records in place. Drug manufacturers are developing high potent drugs, and despite the lack of specific environmental and safety regulations, HPAPIs have become fertile ground for contract manufacturing and for contract development and manufacturing organizations (CDMOs & CMOs for HPAPI manufacturing), which have been actively building up capacity over the past few years. The following critical parameters covering HPAPI development or hi-potency (hi-potent) drug substance development should be considered when choosing a CDMO - contract development and manufacturing organization - partner offering contract development and manufacturing of highly potent APIs to manage shortened development timelines for HPAPI products: - Contract manufacturing Scale - Quality Regime - Pharmaceutical manufacturing (HAPI - High Potent Active Ingredient Manufacturing) - Containment - Formulation & Enabling HPAPI Technology - Devices - Drug Product Supply Once an appropriate CDMO is selected for HPAPI development & manufacturing services, the main features and special facilities required for the handling and development of High Potent APIs (High Potent Active Pharmaceutical Ingredients - HPAPIs) are noted below: 1. Room pressure differentials designed to overcome HAPI containment challenges (with monitoring and verification), with the main HPAPI-handling or highly potent API handling area at negative pressure to surrounding rooms. 2. Airlocks and vestibules around pharmaceutical manufacturing (contract development and manufacturing of highly potent APIs) facility and laboratory spaces to provide gowning and de-gowning areas and proper pressure differentials. 3. Restricted access to ensure that only the necessary trained employees enter the HPAPI-handling areas. 4. Misting showers as part of exit vestibules to rinse personal protective equipment (PPE) and gowning prior to removal. 5. Filtration and capture of contaminants, with safe-change filters, both point source (within the isolator, ventilated enclosure) and the general HVAC exhaust system. Many contract manufacturers are building new facilities that are designed specifically for the manufacture of HPAPIs, which require an investment of millions of dollars beyond typical GMP (good manufacturing practices) production facilities. This investment may include specialized facilities for HPAPI–antibody conjugations that incorporate both handling of high potent APIs and biologics processing capabilities. As in other areas of pharmaceutical manufacturing, in HAPI (High Potent Active Ingredient) manufacturing, disposable or flexible containment technologies are becoming important in HPAPI manufacturing. Automated systems are already in operation across many facilities but this is likely to increase as processes become more integrated. As the demand increases for high potency drugs and development of highly active pharmaceutical ingredients (HAPIs) in biotechnology occur, there is the potential for closed systems to be developed to further protect operator and environment safety, however this will coincide with a reduction in production volumes. In summary, the product development of highly potent drug substances and drug products bring a number of challenges, but they are not insurmountable. Technologies to ensure safe handling procedures have now become widely available (e.g. isolators, split butterfly valves). Q3. What are the processes involved in HPAPI manufacturing from process development to cGMP production? High Potency Active Pharmaceutical Ingredients (HPAPIs) are complex APIs which are highly specific in their action and offer significant efficiency even at low daily therapeutic doses. HPAPIs have the ability to target precise disease cells and are, hence, used in formulating highly potent drugs. The small, medium or large-scale highly potent API (HPAPI) manufacturing at desired levels of quality, requires highly specialized process development capabilities, as well as a broad mix of associated advanced technologies. High potency manufacturing of highly potent compounds can have significant benefits, but they also present multiple challenges to companies offering contract manufacturing services for high potency APIs (HPAPIs) or high potency API (HPAPI) services, especially during commercial operations. The development and transfer of HPAPI manufacturing processes to full production scale presents particular challenges to a CDMO facility or CMO for HPAPI manufacturing. It is especially important to conduct a full risk analysis including setting of Occupational Exposure Limits (OELs) for each high potency chemical step. The procedures currently involved in HPAPI manufacturing encompassing process development & current Good Manufacturing Practice (cGMP) production include: - R&D laboratories (Batch size: From mg to g scale) 1. Analytical & Process transfer / familiarization 2. Process & analytical development of highly active pharmaceutical ingredients (HAPIs) 3. Process characterization 4. DoE (more information – faster – using less product) - Kilolabs (Batch size: From 20g to 500g) 5. cGMP production for clinical trials 6. Process validation 7. Clinical supply Large-scale highly potent API (HPAPI) manufacturing (Batch size: From 500g to 10kg) 8. cGMP production at commercial scale 9. Commercial supply 10. Quality control - Method development / transfer / validation - IPC - Release testing - Stability studies Technological advances will further drive changes in the HPAPI manufacturing process. Given the risks involved with operator exposure to high potency drug products, however, there are certain technologies that we can expect to eliminate the potential risks, which will be incorporated into the manufacturing process — namely the use of robotics that will remove the operator from physically working with harmful substances. Q4. How are containment challenges for highly potent compounds (HPAPIs) handled? Regulatory demand for effective, lower-dose treatments combined with growing incidents of cancer, diabetes, and cardiovascular diseases has seen many pharmaceutical companies focus their R&D investments in HPAPI products. Furthermore, the life cycle of a highly potent or hi-potency (hi-potent) medicinal product is very complex, and therefore there are many issues to be considered to develop containment measures specific for each single case, which have to be based on preliminary risk assessments. If an overall HAPI (High Potent Active Ingredient) manufacturing facility consists of three components — pharmaceutical materials, personnel and the environment surrounding them — containment is the isolation of the first of these components from the other two. Containment, how it is achieved, how it is measured, and how it is maintained are key considerations for any provider handling hi-potent or hi-potency materials. Moreover, high-containment manufacturing requires specialized approaches in facility design, equipment selection and manufacturing processes to overcome HAPI containment challenges, minimize operator exposure, and ensure worker protection and safety. The analysis should always proceed in parallel from three different points of view: the safety of workers, the evaluation of exposure limits and those of the risk of explosion for HPAPI powders. Containment measures thus start from primary ones, related to the characteristics of the equipment used to manipulate the drug substance, and are followed by secondary containment measures, those related to the characteristics of the buildings (i.e. HVAC systems). It is a key regulatory and safety requirement that prospective hazards associated with the handling of HPAPIs are identified and understood to enable the development of Occupational Exposure Limits (OEL). Together with other factors including Short-Term Exposure Limits (STELs) and the physical properties of an API, the definition of an OEL plus associated health risk classifications enable organizations to conduct risk assessments for operators working in HPAPI facilities. These assessments can then be used to establish and maintain safety and containment controls that minimize exposure risk regardless of the manufacturing stage or production site. Conformance to pharmaceutical regulatory requirements and ICH guidelines also requires a thorough consideration of other quality and safety procedures to prevent the release of an HPAPI or intermediates, or cross-contamination with other products manufactured at the site. Following standard risk management and industrial hygiene methodology, it is important to first recognize, evaluate and control the handling of HPAPIs—and to revisit this process periodically, capturing any changes in available product data, manufacturing processes or containment HPAPI technology. For safe handling of highly potent — and often highly toxic — materials, manufacturing practices have moved away from reliance on personal protective equipment (PPE) alone, with current practices focusing on “containment at source,” using isolator technologies, to prevent operator exposure to such compounds during processing. Q5. Which HPAPI development and manufacturing services does Minakem offer? There are various pharmaceutical manufacturers (CDMOs, CMOs for HPAPI manufacturing) that offer custom synthesis and HPAPI development and manufacturing services. Leading pharmaceutical organizations offering HPAPI development & manufacturing services (high potent CDMO services) include Minakem. Minakem Minakem provides fully integrated and technology-oriented contract manufacturing services ranging from process development, kilo lab & pilot scale-up through to full industrial scale manufacturing of complex molecules such as cytotoxic compounds including Highly Potent Active Pharmaceutical Ingredients (HPAPIs) for the Life Sciences and Specialty Chemicals markets. Minakem has a fully GMP compliant and FDA inspected production site that can also provide full regulatory support. Minakem offers custom synthesis, development and current Good Manufacturing Practice (cGMP) manufacturing of High Potency Active Pharmaceutical Ingredients (HPAPIs) and intermediates. Minakem also offers a complete range of custom development and manufacturing services for High Potent Active Pharmaceutical Ingredients - HPAPI (high potent CDMO services), more specifically Minakem offers high potency API (HPAPI) services, custom synthesis from early-stage development to scale-up & commercial manufacture of high potent APIs with occupational exposure limits (OEL) down to 0.1?g/m³/shift (OEB class 6). Minakem thus offers a combination of innovative custom development and manufacturing solutions through a wide range of flexible assets, specialized technologies, and advanced process capabilities and contract manufacturing services for the synthesis of intermediates, APIs, and highly potent drug substances (HPAPIs) at all production scales. Minakem is a leader in certain technologies including flow reactions, hazardous chemistry, HPAPI technology, including cytotoxic compounds, and low-temperature chemistry.

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