API GMP Contract Services | Commercial Manufacturing

Overview of GMP manufacturing & more on leading contract manufacturing organizations (CMOs) offering cGMP contract manufacturing services for APIs.

Q1 What is GMP and what is the importance of GMP manufacturing?

GMP refers to the good manufacturing practice regulations propagated by the US Food and Drug Administration (USFDA) under the authority of the Federal Food, Drug, and Cosmetic Act. These regulations are required to conform to the guidelines recommended by the agencies that control the authorization of the manufacture, sale and licensing of pharmaceutical products, food and beverages, and cosmetics. Different countries have different agencies which regulate pharmaceutical manufacturing activities.

GMP thus constitutes the license to operate in pharmaceutical manufacturing and is a core condition worldwide. Moreover, this system is designed to minimize the risks involved in pharmaceutical production that cannot be eliminated by testing the final product. The main risks are unexpected contamination of products, causing damage to health or even death, incorrect labels on containers, and insufficient or excessive active ingredients, resulting in ineffective treatment.

cGMP refers to the current Good Manufacturing Practice regulations enforced by the FDA. Good Manufacturing Practices (GMP) and current Good Manufacturing Practices (cGMP) are, in most cases, interchangeable, but the “c” in cGMP is added to certify that every step used in the pharmaceutical production process is not only done under the guidelines of GMP, but is also completed in the most current manner available.

Importance of Good Manufacturing Practice (GMP):

It is nearly impossible to determine if a drug or supplement is safe or effective simply by looking at it. This is why GMP is so necessary — GMP guidelines protect consumers from potentially harmful medicines and supplements that they cannot detect themselves. Good Manufacturing Practice (GMP) guidelines aid manufacturers in improving the production of goods.

Furthermore, GMP guidelines help ensure proper design, monitoring, and control of manufacturing processes and facilities. GMP thus comes with strict protocols that lessen the risk of manufacturing errors. The FDA sets the current Good Manufacturing Practices (cGMP), a set of standards that cGMP manufacturers are required to follow and adhere to. These standards and guidelines also ultimately help in maintaining the trust of consumers.

Various pharmaceutical GMP manufacturing organizations, including contract cGMP manufacturers/companies (CMO), facilitate the outsourcing of GMP contract manufacturing services. Contract manufacturers may provide pharmaceutical GMP manufacturing services for APIs and key intermediates and other commercial pharmaceutical products to ensure that products fulfill GMP requirements.

The formulation development team and commercial manufacturing units of cGMP manufacturers work together to optimize formulations. cGMP manufacturers may also offer services to scale up from R&D to cGMP manufacturing of clinical trial materials and commercial pharmaceutical products.

Q2 What are the principles of GMP Manufacturing?

GMP guidelines are created and enforced by national or international regulatory agencies, like the USFDA or the World Health Organization (WHO) in order to protect consumers. GMP production takes into account five key elements, popularly known as the 5 P's of GMP - people, premises, processes, products, and procedures.

For pharmaceutical and other life science disciplines, it is important to focus on GMP compliance to ensure the best quality, consistency, and safety of end products for which the ‘5 principles of GMP manufacturing’, noted below, can be helpful.

5 Principles of GMP Manufacturing:

People

A pharmaceutical GMP manufacturing company is nothing without the people that run its activities. Employees must be trained to follow standard procedures and their performances must be assessed regularly to ensure all employees comply with the current good manufacturing practices that meet an organization's expected standards.

Premises

cGMP facilities should have well-documented cleaning procedures for all their premises and different types of equipment. It is also essential for them to have documented instructions on how to calibrate various equipment.

Processes

Processes should be appropriately documented in a clear and consistent manner, and should be distributed to all employees. Furthermore, processes where the output cannot be fully verified through subsequent monitoring or measuring should be validated. There should be complete documentation surrounding the validation activities as well.

Products

This “P” refers to the final products sold to consumers and the raw materials involved in the formulations. Specifications for raw materials (API and key intermediates) and components must be clear at every phase of cGMP manufacture, and there must be a record of the master formula.

Procedures

All procedures must be regularly revisited to ensure the use of the latest technology and science involved in pharmaceutical GMP manufacturing. If a procedure is using outdated technology, the contract manufacturer may struggle to maintain current Good Manufacturing Practice (cGMP) compliance. Furthermore, the people employed in any manufacturing company must adhere to the rules and procedures for smoother functioning.

Q3 What are the key elements in GMP contract manufacturing?

With the rise in US Food and Drug Administration (FDA) inspections, companies of all types are being audited for current Good Manufacturing Practice (cGMP) compliance, including companies which outsource all manufacturing, packaging, labeling, and holding activities to third parties.

In practice, personnel must be adequately trained, suitable premises and equipment used, correct materials used, approved procedures adopted, suitable storage and transport facilities available, and appropriate records made. The aspects noted below are considered key elements when it comes to pharmaceutical GMP contract manufacturing.

Quality Management

Quality management outlines the general concepts of quality assurance (QA) as well as the principal components or subsystems of GMP, which are the joint responsibilities of top management and of production and quality control management. Quality management focuses on the importance of building quality into products, by systematically controlling component and product-related processes.

Quality Control

One of the most critical components of good manufacturing practice is quality control (QC). It can be defined as the process of sampling, testing, and comparing results with pre-agreed specifications as a part of the overall quality assurance (QA) process.

Personnel

There should be an adequate number of personnel qualified by appropriate education, training, and/or experience to perform and supervise the cGMP manufacture of API and key intermediates.

Contracts

GMP contract manufacturing must be correctly defined. Written contracts must ensure satisfactory quantity and quality requirements.

Documentation

All documents related to the cGMP manufacture of API and key intermediates should be prepared, reviewed, approved, and distributed according to written standard procedures.

Premises & Equipment

Laboratories must maintain uniform premises and equipment. Equipment used in the cGMP manufacture of API and key intermediates should be of appropriate design and adequate size, and suitably located for its intended use. Furthermore, they should be cleaned, sanitized and maintained appropriately.

Self Inspection

Audits are a way of inspecting systems to ensure that they are being carried out correctly when compared to pre-qualified ‘standards’.

Production & Process Controls

Companies must implement a system whereby they ensure products are produced, packaged, and labeled as per GMP compliance guidelines.

Purchasing

Purchasing includes parameters like specifications, quantities, and delivery times. Companies must verify these parameters related to the quality of incoming goods.

Complaints & Recall

Complaint records should include the name and address of the complainant, the phone number of the person submitting the complaint, the nature of the complaint (including name and batch number of the API), and the date when the complaint is received.

cGMP manufacturers/companies (CMO) provide GMP contract manufacturing services which may help small and mid-sized pharmaceutical companies from drug development all the way through to drug manufacturing. In addition, some organizations offer formulation development and GMP production services for complex APIs and key intermediates.

Q 4 What are the advantages of working with an embedded CMO offering API GMP manufacturing services?

To produce a drug, different kinds of resources are needed. A company may not find all of these resources in its own country and can outsource such cGMP manufacturing services to a country where these resources are readily available. Companies that outsource manufacturing can cut labor costs, including salaries for personnel, overhead, equipment, and technology.

Pharma companies often need to access specialized GMP manufacturing resources, facilities, and capabilities to progress a drug from development to commercial production. Thus, pharmaceutical developers can bring a product to market in two ways: by manufacturing it in their own facilities; or by procuring and buying capacity from a contract manufacturing organization (CMO).

Currently, the outsourcing market is extremely fragmented – from smaller, specialized CMOs and full-service, end-to-end contract development and manufacturing organizations (CDMOs) to ‘pure play’ and embedded outsourcing models.

Businesses operating as embedded contract manufacturing organizations (CMOs) are self-contained organizations that work within larger companies. They use all the assets and resources of a larger company to manufacture API and key intermediates and other pharmaceutical drug products for their partners.

Some Advantages of Working with an Embedded CMO Offering API GMP Manufacturing Services:

Growth

A capacity-filling-only model can be precarious for biopharmaceutical companies, which require a steady, long-term CMO partner. A primary advantage of an embedded contract manufacturing organization (CMO) is that it operates to a business model built to support strategic growth.

Quality Assurance

Contract manufacturing organizations (CMOs) have pre-established quality checks in place that have been refined over the years. cGMP manufacturers have to ensure that they are manufacturing API and key intermediates in GMP compliance with various standards used in different countries.

Global Network

Working with an embedded contract manufacturing organization (CMOs) gives customers access to the people and advanced science that are used by the parent organization to bring innovative commercial drug products to market.

Direct Engagement for Long-term Planning

A contract manufacturing organization (CMO) is an integral part of the organization’s operations team, giving it a direct line to key decision-makers within the wider organization. As a result, any issues are raised and dealt with readily, at a company-wide level when necessary.

Scalability

As a small business or start-up, it’s challenging to scale products with limited resources at hand. Since contract manufacturers have more resources, they are more than able to scale products.

World-Class Operations and Sustained Investment

An embedded CMO’s strategic value is also contingent on the quality of its facilities, and devotion to technical innovation.

A cGMP manufacturer may offer contract services in accordance with current Good Manufacturing Practice (cGMP) guidelines. Some contract development and manufacturing organizations (CDMOs) have several years of experience that have enabled them to gain niche expertise in drug manufacturing and formulation development, along with the expertise to scale up from R&D to cGMP manufacturing. In addition, contract cGMP manufacturers/companies (CMO) may offer a broad range of GMP production services for the pharmaceutical industry and ensure that all commercial pharmaceutical products comply with cGMP requirements.

Q5 Which are the leading pharmaceutical companies offering GMP contract manufacturing for APIs?

Various GMP contract manufacturers, including contract development and manufacturing organizations (CDMOs), may have experience in producing API and key intermediates and drug manufacturing. Such CMOs and CDMOs can offer cGMP manufacturing services for the biotechnology and pharmaceutical industry as per cGMP requirements.

These organizations might have years of experience in developing commercial pharmaceutical products along with clinical trial materials via GMP manufacturing. Some of the top contract manufacturing organizations (CMOs) and contract development and manufacturing organizations (CDMOs) with GMP contract manufacturing capabilities are explored below.

Leading cGMP Manufacturers Offering GMP Contract Manufacturing Services:

Interquim SA - GMP Manufacturing

Interquim's quality system is governed by good manufacturing practices (GMP) and continual improvement. Their quality system and installations have been inspected and approved by regulatory bodies and clients, who demand the highest standards.

PMC Isochem - GMP Manufacturing

PMC Isochem operates 3 cGMP manufacturing sites for the production of API and key intermediates, excipients such as tocophersolan (Vitamin E TPGS), and amino acid polymers. PMC Isochem offers cGMP and non-cGMP industrial exclusive custom synthesis and provides tailor-made services, from development to production, including route selection, process and analytical development, clinical trial materials GMP manufacturing as well as process optimization.

Pfizer CentreOne - cGMP API Manufacturing

Pfizer's pilot cGMP manufacturing facility has the flexibility to support small clinical or commercial batches. They provide commercial manufacturing services for large biologic molecules, solid oral doses, and sterile injectables along with GMP manufacturing of clinical trial materials. Its manufacturing site in Kalamazoo focuses on producing API and key intermediates for branded medicines.

Minakem - cGMP API Manufacturing

Minakem's Beuvry-la-Forêt site has over 40 years of experience and expertise in fine organic and pharmaceutical chemistry, and offers cGMP manufacturing services for API and key intermediates, regulatory starting materials, and building blocks. They also provide commercial manufacturing services, including scale up from R&D to cGMP manufacturing.

Farmak A.S - GMP Compliant Manufacturing

Farmak offers production in GMP compliance with the current good manufacturing practice (cGMP) and ISO systems from several production modules. Their manufacturing facilities are capable of a batch size from 100 g up to several kilograms (kilo lab) and from 5 kg to 250 kg in reactors.