Revisit Required: Good Documentation Practices (GDP) - Most underrated GxP
GxP is an acronym for the group of good practice guides governing the preclinical, clinical, manufacturing and post-market activities for regulated pharmaceuticals, biologics, medical devices, etc., such as good laboratory practices, good clinical practices, good manufacturing practices and good distribution practices. We usually give emphasis on conducting various trainings related to GCP, GLP, GCLP and GMP, conducting various workshops, online trainings and conferences. Our job descriptions mandates various trainings associated with our profile and refresh it at yearly or even shorter intervals. What we usually overlook is sheer basic training irrespective our profile, designation or position in the institution. We forget that, from Day 1, we join any organization, starting from acceptance of offer letter, we need to get ourselves train in that area.
What’s that Watson? Documentation my dear Holmes! Document is any written statement or proof of any activity in pharmaceuticals. Documentations are to define the manufacturers system of information & control, to minimize the risk of misinterpretation & errors inherent in oral or casually written communication, to provide unambiguous procedures to be followed to provide confirmation of performance, to allow calculations to be checked & to allow tracing of batch history. Documents are a mirror to show actual image of any pharmaceutical company. Expertise in documentation is the key to successful regulatory road map. Good Documentation Practices (GDP) are methods for recording, correcting and managing data, documents and records, to ensure the reliability and integrity of information and data throughout all aspects of a product’s lifecycle . Concepts of Data Integrity (DI) and GDP are interrelated. Data integrity is the degree to which a collection of data is complete, consistent and accurate throughout the data lifecycle. The collected data shall be attributable, legible, contemporaneously recorded, be an original or a true copy, and accurate.
Concept not new, but “Data Integrity has been and currently is a major global concern of Health Authorities and the pharmaceutical industry.” In 2016, 80% of FDA warning letters issued had Data Integrity deficiencies. In fact, the FDA cited DI on 79% of the Drug Warning Letters over the last 5 years, and they have increased the number of Warning Letters citing DI by over four times. As discovered in other CDER enforcement trend analysis, Asia consistently receives more citations for data integrity than any other region. This could be a result of the increasing inspection in Asia by the FDA after the United States Government Accountability Office report on international inspections not keeping up with the increasing number of drugs and active ingredients coming from Asia. All big and small pharmaceutical companies are affected in same manner.
Leave aside GCP, talking about most common GMP inspection warning letters, sites in ‘Asia’ (Japan, China, India, Taiwan and Hong Kong) account for approximately 71% of drug GMP warning letters issued outside the U.S., the same as the percentage over the six year period FY2013 – FY2018.
73 warning letters were issued regarding sites outside the U.S., and 47 of these had associated import alerts for failure to comply with drug GMPs or refusal of an inspection. So not only did 64% of firms that received warning letters have the expense associated with remediation of the warning letter itself, they are prevented from selling product from these sites in the U.S., excluding FDA-identified medically necessary products.
Chinese pharma companies received 24 warning letters and 21 of these also were placed on import alert. China, India, and Korea taken together, account for 68% of the import alerts associated with warning letters. Each country likely had additional sites that were the subject of import alerts, but these were not associated with warning letters. Data integrity deficiencies in warning letters continue to identify the predicate rule(s) to which firms did not adhere.
What is takeaway?
As the manufacturer (product sponsor), organisation is ultimately responsible for ensuring EVERY person involved in the production, distribution and assessment of products has attained appropriate Good Documentation Practices compliance training (with proof, e.g. assessments/training certificates).
- All people who have contact with product, at any stage of production, delivery or assessment (pre-clinical or clinical inclusive staff of clinical trial sites), need to have evidence of GDP training and regular compliance assessments.
- Areas to focus: ALCOA ( Attributable, Legible, Contemporaneous, Original and Accurate ), PDCA (Plan, Do, Check, Act) for data integrity
- Self-Inspections for GDocP (GxP) compliance