Is there a Pre-Approval Inspection (PAI)? When will it be? Will our site be inspected? The anxiety-tinged queries from production (and management) personnel start almost as soon as an application is submitted, and until now regulatory personnel had little answers to offer except vague reassurances like, “We have to wait and see” or “It’s up to OPQ”.
Donald Ashley, JD, Director of the Office of Compliance at CDER reported a rather surprising statistic relative to the country that received the most warning letters in FY 2019! And the winner is – the United States! Domestic firms received 54 warning letters, followed by India with 17 and China with 14. Previous years had India or China with the dubious distinction of being issued the most warning letters.
In two separate Federal Register (FR) Notices on the FR prepublication page (here and here), the FDA proposed to withdraw approval of two ANDAs based on lack of confidence in the bioequivalence data contained in the applications. The concern relates to a problem at a bioequivalence testing laboratory. The Notices state:
“In May 2010 and December 2010,
The FDA issued a revised draft guidance titled “Drug Products Labeled as Homeopathic Guidance for FDA Staff and Industry” (here) describing the FDA’s proposed risk-based enforcement approach to homeopathic products. This compliance guidance represents current Agency thinking after comments were reviewed based on the initial guidance (here) that was issued in December 2017.
In thinking about the current vaping issues, which have been associated with a significant number of deaths and hundreds, if not thousands, of lung-related injuries, I think the path to the future of these products needs to be critically evaluated by the FDA. The introduction of e-cig came so fast that the FDA was not prepared to deal with the issue.
The use of alternate methods, especially for USP methods, some of which are rather old, has long been a question that both the industry and the FDA have contemplated. Alternate methods can be easier to use and, in some instances, more accurate and reliable. But how can you demonstrate that an alternate method is indeed equivalent to an existing method?
In a short Warning Letter issued by the FDA on August 29, 2019, the Agency informed a China-based testing firm that, because it refused inspection, that FDA would withhold approvals of any ANDA or NDA in which it was cited as a testing laboratory. The FDA takes refusal of inspection very seriously and the impact on NDA or ANDA sponsors (or,
For all Sponsors submitting INDs, NDAs, ANDAs, BLAs, and supplements, and the bioanalytical laboratories analyzing and reporting the data to support these submissions, the FDA just issued its Guidance for Industry, “Evaluation of Internal Standard Responses During Chromatographic Bioanalysis: Questions and Answers.” The Q&A guidance contains five questions, along with the Agency’s current thinking on each topic.
It is paramount that a Quality Control laboratory has a calibration and preventative maintenance program for the laboratory instrumentation so that there is assurance that the instrumentation continues to be “fit for purpose” and that there is confidence in the accuracy and reliability of all analytical instruments. There should be a controlled, comprehensive list of the instrumentation within the laboratory,
Take action now to assure that your facility information, drug listing information, and manufacturing sites are correct and that no changes have been made to any of these items or others that are listed in the FR notice due to publish on Wednesday (pre-publication notice here).
The Notice indicates registrant’s responsibilities as follows:
Each registrant must list all drugs it manufactures for commercial distribution within 3 days of initial registration (21 CFR 207.45).
It certainly seems that the world is getting smaller and this concept has been coming to the regulated industry for quite some time now. As early as 1999, the European Commission has been working diligently with the EMA and other regulatory bodies throughout the world to form Mutual Recognition Agreements (MRAs) related to inspections and to harmonize standards within the industry.
We are living in a world that is constantly changing and using forms of media such as videos and live recordings as forms of communication, notification, training and archiving of special events. In this age, we are constantly bombarded with Tweets, G-Chats and Facebook posts that have videos attached. We can stream tv shows, live news reporting and sports events in real time.
Like death and taxes, eventually every pharmaceutical testing laboratory will get a regulatory agency inspection. The anticipation of a regulatory inspection will instill great angst even within the most compliant laboratories. The anticipated inspection might be a periodic inspection, but most often is a Pre-Approval Inspection (PAI). The anxiety about an impending inspection often triggers a request for an independent third-party audit of the facility including the laboratory.
The Report issued each year by the Office of Compliance (OC) is a treasure trove of facts and figures espousing the accomplishments of the OC. The 32 page document (which can be found here) provides a detailed account of OC actions in the enforcement arena, guidance area, consumer awareness and education area,