What exactly do pharmaceutical GMP regulators and inspectors around the world want to see? We take a look at the latest trends and real world findings so you can align yourselves with the tastes of compliance regulators.
Rising expectations and scrutiny from regulators have undoubtedly developed the quality of how medicines are manufactured.
Use this round-up to align with the Good Manufacturing Practices (GMP) expectations of regulators by learning from peers and the latest advances.
GMP updates
Australia: The TGA on the first of January enforced new manufacturing requirements for medicine producers. The authority is phasing its on-site inspections for the new standards. The transition period is expected to last until 1st January 2019. Transition timelines can be viewed here.
Brazil: ANVISA recently released a new regulation expected to transform the nation’s GMP inspection and certification measures.
US: The FDA announced 98 draft guidance documents due to be published in 2018. Two were listed under pharmaceutical quality manufacturing standards one being Guidance for Human Drug Compounding Outsourcing Facilities.
In a move to reduce exertion of inspection resources and avoid duplication, the US FDA extended permission to four EU states – Czech Republic, Greece, Hungary and Romania to conduct FDA level GMP inspections by July 2019.
India: Recent reports emerged stating the Drug Controller General of India (DCGI) may blacklist multiple Chinese API firms.
UK: The national medical regulator clarified the latest with negotiations between the UK and EU that there are no sudden changes to compliance requirements as a result of Brexit.
China: China and the UK finalised a memorandum of understanding in an effort to solidify international relationships to strengthen medical regulatory systems.
EU: The EU published a report detailing the implementation of the Falsified Medicines Directive (FMD). The majority of EU member states have introduced penalties attached to breaching FMD law vary from imprisonment, fines and administrative sanctions. The maximum prison sentence is three years.
GMP Findings
Nigeria: In January and February the National Agency for Food and Drug Administration and Control (NAFDAC) confiscated over 40 container loads of drug substances. The controlled drugs, mostly Tramadol, were seized at a range of seaports across the country.
Pakistan: Over the last three years, the Drug Regulatory Authority of Pakistan (DRAP) initiated the testing of 171,000 samples at laboratories in its campaign against spurious drugs.
Last year, the authority launched 1,452 drug court cases within a nine month period, 884 reached decisions of which eight drug manufacturing licenses were suspended/cancelled.
The same period saw 784 GMP inspections take place.
Denmark: After an inspection in December, the Danish Medicine Agency filed a statement of non GMP compliance against Kadam Exports Private Ltd of 205-207, G.I.D.C. Estate, Mehsana, Gujarat, India.
The quality of the product the Active Pharmaceutical Ingredient (API) Psyllium HUSK – used in dietary and herbal medicinal products, was not ensured as far as the agency was concerned. The unit was deemed to lack the ability to meet GMP principles in production as well as within its laboratory, leading to a big risk of contamination. Staff were not trained in EU GMP guidelines and reference and retention samples were not stored in controlled containers.
US: In one week, the FDA published a round of warning letters depicting significant GMP violations regarding finished pharmaceuticals. Some of the main observations included:
Shanwei Honghui Daily Appliance Co., Ltd. Shanwei, China:
- “Based on photographic evidence collected by our investigator, your filling machines used to manufacture over the counter (OTC) drug products for the U.S. market were filthy and were surrounded by cardboard and dirty rags. Your firm also failed to sanitize your (b)(4) system since its installation more than 10 years ago.”
- Failure to provide batch records after the investigator was informed there was not a record for each batch.
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Delta Laboratories Pty. Ltd., New South Wales, Australia:
- Failures to thoroughly investigate release and testing stability failures regarding viscosity and appearance of the medicinal product. Satisfactory quality investigations were also not launched when packaging defects were found in stability testing.
- Lacking process validation studies to ensure medicines are consistent and reliable in quality and purity.
Updates in what GMP inspectors want to see
Stickers for unique identifiers: FMD requirements from the EU state that in cases where manufacturers have no feasible alternative and are authorized to do so by national authorities, a unique identifier can be placed as a sticker on outer/immediate packaging but has to be applied by a manufacturer under GMP conditions. Also the sticker must become one with the packaging and be tamper evident.
GMP assessments for Australian government: By 1st July of 2018 manufacturers should have completed assessments on how new manufacturing principles will impact operations. Firms should be nearly finished with updates to quality systems documentation or have adequate justifications for their lack of progress. Transition timelines can be viewed here
Making a change? Let the regulators know: The Danish Regulatory Agency put out a statement regarding manufacturers that wish make alterations, for example to advance to produce new formulations or relocate, these firms need to apply for authorization from the Agency.