Market Place
Last week, Speak Pharma carried the views of Peter Werth, President and Chief Executive Officer, ChemWerth, who spoke at length about how data integrity has no relationship with product quality. This week, we have another personality – Peter Saxon, a manufacturing compliance specialist who runs a 23-year old consulting practice in the US. Most of Saxon’s clients are based in Asia. Saxon speaks about how FDA’s ‘hot topics’ have evolved over the years. He shares some of Werth’s views on data integrity.
Saxon has worked in both chemical and finished dosage operations in the pharmaceutical industry, in the US, Egypt and Switzerland. In addition to preparing companies for US Food and Drug Administration (FDA), Therapeutic Goods Administration (TGA) and European Directorate for the Quality of Medicines & HealthCare (EDQM) inspections, Saxon also performs third party audits.
- Tell us about your experience in assisting companies with understanding GMP standards and upgrading them to even higher GMP standards in the last 20 years.
When I first started assisting Asian companies, the understanding of regulatory GMP was non-existent. For example, most Chinese companies believed that once the Drug Master File (DMF) was filed and they received a DMF number from the FDA, the work was done. And they could celebrate and start selling APIs to the USA. There was also a common belief that no Chinese company could ever pass an FDA inspection.
- How have compliance standards in India and China evolved over this time period?
The process of evolution of companies in India and China had to move much faster than the GMP requirements set by regulatory agencies (such as US FDA, TGA and EDQM).
Earlier, US FDA inspections usually involved one inspector visiting the site every four to five years. These days, two FDA inspectors visit the manufacturing site for five days every two years. Therefore, the man-day coverage has increased almost four times.
There are hardly any significant regulatory changes. But the interpretation of regulation has tightened significantly. For example, the definition of testing into compliance has become more encompassing and more clearly defined with the issuance of the OOS (out of specification) guidelines.
- How has the FDA’s approach towards inspections changed during this period?
The FDA got more focused and impactful about some meaningful topics, or ‘hot topics’ as I choose to call them. For example, in 2000, label control and its content was a big concern. By 2003, identifying the root cause took priority. In 2006, there was more focus on CAPA (corrective and preventive action) procedures. In 2014, supplier audit and vendor qualification was included in every inspection. In 2015, data integrity became a hot topic. And in 2016, internal audit verification has become important.
Data integrity rose to the surface when the FDA found companies deleting or overwriting testing results to hide (failing) results and thus releasing the failing product.
Most ‘incidences’ found in the instrument data trail are acceptable occurrences, as pointed out by Werth in last week’s Speak Pharma. I agree they have nothing to do with product quality.
In my opinion, data integrity is over-stated by many consultants and FDA investigators, since they lack sufficient understanding of our business and the data integrity requirements for cGMP.
Two years from now, all companies will install full audit trail software that is compliant and the next GMP issue will come to the surface.
- In your view, why do companies fall into the data-integrity trap? Does the failure to perform root cause analysis land them in this trap?
Most inspection observations (Form 483 issued by the FDA) arise because the quality control departments do not do a good job of auditing instrument history and noting incidences, discrepancies and deviations.
Lack of understanding, over-reaction and perhaps some guilt are behind data integrity violations. Of course if you are overwriting or deleting unacceptable results, it is a deliberate exercise. It is not a trap. Such companies deserve FDA’s Form 483 observations.
However, if a company does not take time to document the acceptable reasons to have an incident, find the root cause and correct the situation, it is contributing to its own regulatory problems.
- How can companies improve their approach towards GMP?
You need to know your business! The hardest concept for me to clarify with any company is identifying the root cause. It is natural for the mind to look at the problem (such as a broken pump) and jump to the conclusion that this is the root cause. If you do not go any further and try to find out why the pump failed, you are ensuring that it will happen again. And, you will waste time without really improving your quality system.
If a company finds its system cumbersome and counterproductive to its needs, it is time to take stock of its overall quality system. I use an approach called ‘zero based cGMP’ to simplify over complicated procedures that have evolved over the years.
You write to Peter Saxon at saxonia1@aol.com.
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