- Coined By: – Stan Woollen in Early 1990s.
- It is a critical aspect to the design, implementation and usage of any system which stores, processes, or retrieves data. The term Data Integrity is pretty widely used and has different meanings in different contexts. The term itself is pretty old and was initially used in computing. The integrity of the data collected and recorded by pharmaceutical manufacturers is critical to ensuring that high quality and safe products are produced. To ensure the integrity of data, it should be protected from accidental or intentional modifications, falsification and deletion.
- With many processes in the process industry, you cannot just simply test the final product to see if it is a proper one. Instead you must assure that the conditions during the process are correct in order for it to produce the correct product. These critical conditions must naturally be recorded and maintained to assure they were correct. This is certainly the case in many processes in a pharmaceutical plant.
History of Data Integrity Focus:
- This focus on the history of data integrity represents an evolution over the past 30-plus years and addresses both changes in technology and learning from GMP inspections. Assurance of data integrity is a component of the larger category of data management and applies equally to paper records and electronic records.
- The “generics scandal” of the 1980’s- raised the issue of falsified data submitted to FDA in support of drug approvals. One outcome of this scandal was the shift in focus of the FDA pre-approval inspection (PAI) to evaluate raw laboratory data included in the marketing application and evaluate whether the site was capable of manufacture as described in the application. This scandal also prompted implementation of the Application Integrity Policy in 1991 which “describes the Agency’s approach regarding the review of applications that may be affected by wrongful acts that raise significant questions regarding data reliability”
- In parallel, FDA recognized the increased reliance on computerized systems within the pharmaceutical industry. To raise that interest –they have developed and published 21 CFR Part 11; the final rule on Electronic Records and Electronic Signatures in
- In 2003: FDA published Guidance for Industry- Part 11 related to Electronic Records; Electronic Signatures – Scope and Application to address enforcement priorities. FDA continues to communicate their interpretations in compliance actions such as forms 483 and warning letters, podium presentations and on their GMP Q&A web site page.
- Warning Letters: In 2000, a warning letter issued to Schein Pharmaceuticals cited lack of control over computerized laboratory systems including; lack of password control and broad ranging staff authority to change data. FDA issued a 15-page form 483 to Able Laboratories in New Jersey in 2005. Three warning letters were issued to two Ranbaxy sites in 2006 and 2008.
- Based on these compliance actions, FDA announced a pilot program in 2010; to evaluate data integrity as part of routine GMP inspections. FDA planned to use the information gained from these inspections to determine whether revisions to Part 11 or additional guidance on the topic were necessary.
- MHRA (Medicines & Healthcare products Regulatory Agency in UK) has recently released new guide “GMP Data Integrity Definitions and Guidance for Industry” (March 2015). There is a deadline set for pharmaceutical companies to comply at the end of 2017.FDA has released “Data Integrity and Compliance with CGMP – Guidance for Industry” (April 2016). This is still in draft mode but has been on comment rounds. Both of these will naturally have effect with the pharmaceutical industry. Sure already before there has been guidance for the good manufacturing practice (CGMP), such as 21 CFR parts (210, 211, and 212), discussing data integrity related issues, but these mentioned new regulation updates will raise the focus.
- New regulation for product packaging to avoid fraud drugs:
- To better control fraud drugs, the European Medicines Agency (EMA) has recently introduced a new regulation that will require all prescription drug makers in all (but three) EU (European Union) countries to incorporate new safety features on their product packaging by February 2019. The regulation, which is part of a broader effort to combat falsified medicines in the EU, will require drug makers to add a unique identifier and an anti-tampering device to the packaging of most centrally authorized products. This naturally ads another burden and cost for the drug manufacturers, to build the systems to support this, but this will certainly be beneficial for the customers. Although this specific regulation is for the European Union area, it will have effect globally.
Reason for Establishing ALCOA:
- Due to the rise in cGMP violations involving data integrity during regulatory inspections, there have been issuances of many warning letters, import alerts and consent decrees.
- Increase the use of mobile devices in calibration processes.
- Data Integrity Issues Occurs In:
- Quality control laboratories and production areas.
- Causes vary due to personnel, equipment and management.
Consent to be followed:
Electronic signature and record-keeping requirements are mentioned in 21 CFR Part 11 and apply to certain records, subject to records requirements set forth in Agency regulations, including parts 210, 211, and 212. Further, regulations for data integrity have been laid out by the Medical Health and Regulatory agency (MHRA) and Pharmaceutical Inspection Convention (PIC/S).
- The implementation of regulatory guidelines and standard operating procedures for data integrity, regular internal audits or surveillances and training will pave way for pharmaceutical industries to maintain data integrity flawlessly.
- A commonly used acronym for “attributable, legible, contemporaneous, original and accurate”, which puts additional emphasis on the attributes of being complete, consistent, enduring and available – implicit basic ALCOA
- We rely on this industry standard initialism known as ALCOA, which has been expanded on to ALCOA+ (currently used by the FDA, WHO, PIC/S and GAMP – Data Integrity), this neatly requires all datato have the following qualities:
- Attributable— Who acquired the data or performed an action and when?
- Legible— can you read the data and any entries?
- Contemporaneous— documented at the time of the activity.
- Original— A written printout or observation or a certified copy thereof.
- Accurate— No errors or editing without documented amendments.
- Complete— all data including any repeat or reanalysis performed on the sample.
- Consistent— all elements of the analysis such as the sequence of events follow on and are date or time stamped in the expected sequence.
- Enduring— not recorded on the back of envelopes, cigarette packets, sticky notes, or the sleeves of a coat but in notebooks or electronic media in the data systems of instruments.
- Available— can be accessed for review and audit or inspection over the lifetime of the record.
Based on these attributes being adhered to the data can be trusted, this becomes both simpler and more complicated when we introduce electronic systems capable of managing all these attributes as part of the ‘meta-data’ and have to consider how we can retrieve, store and archive data across its entire life cycle.