Typical PQS deficiencies found at drug manufacturers: what does a GMP inspection focus on?

The topic of the pharmaceutical quality system being an integral part of the entire drug manufacturing process, the peculiarities of its implementation and data integrity were discussed this day at the «RegLec-EAEU» conference by the regulators and pharmaceutical manufacturers both from Russia and from other countries.

The Head of the Drug Manufacture Inspections Department Ms. Ekaterina Nikiforova, based on the experience of SID & GP in inspections of drug manufacturing sites for compliance with Good Manufacturing Practice, noted that the pharmaceutical quality system stipulated in GMP Chapter 1 is the second most frequently discovered among critical deficiencies and the forth – among major deficiencies for inspections in 2018.

Among the main deficiencies in the field of PQS impacting the quality of drugs and consequently resulting in potential harm to a patient’s life and health Ms. Ekaterina Nikiforova noted the following:

• The manufacturer does not guarantee drug product release according to the requirements of the RF normative documentation. There is no change control including notification to the Russian regulatory authority about the changes introduced.
• The steps of drug product manufacture are executed at the manufacturing site which is not listed in the Marketing Authorization.
• The assessment of the quality of finished products (for non-sterile solid dosage forms) and issuance of the release permit are done based on quality control of in-bulk products. The finished product in final packaging is not controlled.
• PQS does not guarantee performance of investigations of deviations and complaints with identification of their root causes.
• Audits of suppliers of raw materials and excipients are not conducted or the frequency of such audits is not justified.
• No periodic reviews are performed for the pharmaceutical quality system with the aim of continuous improvement of products, processes and the system itself.

«Unfortunately, there are cases when the manufacturer uses a pharmaceutical ingredient which is not listed in the registration file for this product,» Ms. Ekaterina Nikiforova told the audience of the conference.

Answering the questions from the audience about repeated inspections, the representative of SID & GP said that, as of the current date, there were 1,966 inspections in the schedule for 2019, as well as some inspections aimed at extending the validity period of the GMP compliance statement issued. With that, SID & GP can carry out inspections of the sites which were refused issuance of a GMP compliance statement.

«Unfortunately, in the market, we see a trend that manufacturers consider minor observations as comments by inspectors and do not rectify them in a proper way. If, during a repeated inspection, we find the same deficiencies, we may re-classify them into «major» or «critical» ones,» Ms. Ekaterina Nikiforova said.