Why Pharmaceutical Data Integrity Is More Important Than Ever

Home / Articles / 2017 / Why Pharmaceutical Data Integrity Is More Important Than Ever Why Pharmaceutical Data Integrity Is More Important Than Ever

With radical pharmaceutical industry changes in the air, the importance of data integrity and the steps the pharmaceutical industry must take are clear.

By Ashley Ruth, Senior Consultant, Analytical Services, BioTechLogic, Inc.

The pharmaceutical and biopharmaceutical industries must give immediate and strategic consideration to data integrity practices for two critical reasons:

  1. increased attention to data integrity shortcomings by global regulatory agencies and
  2. the possibility of a less stringent regulatory environment.

To understand the pressing ramifications of the data integrity issue, we must remind ourselves that data is both the backbone of CGMP compliance and the fuel of the digital economy. In the pursuit of increased efficiency, digital approaches are being used for risk reduction and greater innovation in pharmaceutical lifecycle processes—from discovery to commercial manufacturing—and must continue to be further leveraged. Additionally, data must become less siloed and flow much more seamlessly throughout pharmaceutical organizations at various stages of the product lifecycle. However, just as if gasoline in a car engine is contaminated, it will damage and/or cease the engine, the same is true for “digital fuel.” Correct and uncorrupted data must flow through a pharmaceutical organization so that correct and reliable decisions can be made.

Even without sophisticated digital data management considerations, data integrity of even the most basic data systems must be assured to ensure compliance.


For several years, the FDA and other global regulatory bodies have emphasized the importance of accurate and reliable data in assuring drug safety and quality. However, in tandem with increased digital sophistication and the role of global manufacturing partners, data integrity violations have been on the rise.

As a reflection of the importance of this issue, in April, 2016, the FDA released draft guidance, “Data Integrity and Compliance With CGMP Guidance for Industry.” Within the guidance itself, the FDA notes the trend of increasing data integrity violations.

The guidance states, “In recent years, FDA has increasingly observed CGMP violations involving data integrity during CGMP inspections. This is troubling because ensuring data integrity is an important component of industry’s responsibility to ensure the safety, efficacy, and quality of drugs and of FDA’s ability to protect the public health. These data integrity-related CGMP violations have led to numerous regulatory actions, including warning letters, import alerts, and consent decrees.”

The phrase “data integrity” often conjures the image of intended and dishonest manipulation of data to achieve some benefit or avoid negative consequences. While purposeful data adulterations do occur, many data integrity violations are not purposeful and are a result of improper training, ineffective SOPs, corrupt systems, or lack of clarity within the regulations themselves. The CGMP framework recognizes that technologies and approaches evolve over time which reflects advances in innovation. Therefore, regulations and guidance are created with built-in flexibility to accommodate these changes. However, often these accommodations result in a lack of clarity.


President Trump has vowed to overhaul the FDA and sharply reduce the regulatory burdens of the current drug approval system. In fact, arguments have been made, by people associated with the administration, to completely eliminate pre-market approval clinical trials that are currently required to demonstrate drug efficacy and safety. Continue reading article

Date Integrity CTA

Live from the PDA Annual Meeting: Risk Management in Combination Products and Co-Packaged Kits

Tracy Speaking PDA 2017

From post-aging performance testing to container closure integrity, robust design controls extend far beyond “constituent part” requirements.

With the increase in complexity of some combination products and co-packaged kits, the need remains for ensuring that the patient gets the right drug at the right dose at the right time. While it is acceptable to make improvements to products as more information becomes available, it’s important to recognize that a change to a co-packaged kit can result in a warning letter if design controls are not properly implemented.

In her presentation at the 2017 PDA Annual Meeting in Anaheim, CA, Tracy TreDenick, Head of Regulatory and Quality Assurance and Founding Partner at BioTechLogic, explained that design controls for co-packaged kits include requirements for individual constituent parts, but also include inter-component dimensional and functional specifications, system integration verification testing and shipping of aged components. “FDA is asking for dimensional and functional specs for the final finished form,” she said.

This is not just about the closure of a prefilled syringe, but about the biocompatibility of all parts combined. She noted, “The challenge is understanding the constituent parts and the system integration requirements.” Continue Reading Article

4 Things You Need to Know About Combination Drug Compliance

Pharmaceutical Processing Combination Drug StoryCombination products are a fascinating area of the pharmaceutical industry and present great future promise. The segment is projected to reach $115 billion in global sales by the end of 2019. It has grown solidly at a rate of 7.9% CAGR since 2013, and is projected to continue at that rate through 2019.1

Some of the key factors driving this growth include: higher levels of patient compliance, demand for minimally invasive surgeries, opportunities for precise pain relief, quicker healing and governments and non-governmental organizations (NGO) embracing combination drugs for their ease of administration.

Combination products defined in 21 CFR 3.2(e)2 are therapeutic and diagnostic products that are composed of any combination of a drug, device, or biological products, with the intention of creating safer, more effective, precisely targeted and easier to administrate therapies.

While the technologies and innovations driving the combination product market deliver a great deal of value to patients and to the medical community, the novelty of these products is often challenging for drug developers and regulatory agencies. The marriage of two different disciplines – drug and medical device – creates a complex regulatory process that must be well managed. In addition, evolving regulations as the combination product segment matures can present challenges for older, legacy combination products. Continue Reading

4 Things Your Need to Know About Combination Drug Compliance



SEE ALSO: The Formation of the Combination Products Policy Council to Improve Regulatory Efficiency

Pharmaceutical Data Integrity Library of Resources

Pharmaceutical Data Integrity Library of Resources

The issue of pharmaceutical data integrity is more important than it has ever been. Data is both the backbone of CGMP compliance and the fuel of the digital economy. Secondly, global regulatory bodies have become increasingly focused on data integrity and have issued many actions of varying severity.

The following collection of resources are the leading guidances and resources for pharmaceutical data integrity.

FDA Draft Guidance: Data Integrity and Compliance With CGMP Guidance for Industry

The purpose of this guidance is to clarify the role of data integrity in current good manufacturing practice (CGMP) for drugs, as required in 21 CFR parts 210, 211, and 212. Part 210 covers Current Good Manufacturing Practice in Manufacturing, Processing, Packing, or Holding of Drugs; General; part 211 covers Current Good Manufacturing Practice for Finished Pharmaceuticals; and part 212 covers Current Good Manufacturing Practice for Positron Emission Tomography Drugs. This guidance provides the Agency’s current thinking on the creation and handling of data in accordance with CGMP requirements. Access Guidance

MHRA GxP Data Integrity Definitions and Guidance for Industry

The United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) guidance on data integrity is one of the globe’s leading resources on the topic. Access Guidance

Elements of a Code of Conduct for Data Integrity in the Pharmaceutical Industry

The Parenteral Drug Association’s (PDA) Elements of a Code of Conduct for Data Integrity in the Pharmaceutical Industry outlines key elements necessary to help ensure the reliability and integrity of information and data throughout all aspects of a product’s lifecycle. It is intended to be used in whole or in part to guide a company’s internal practices, create or modify an existing data integrity code of conduct, or in developing agreements with outsourcing partners or other suppliers. The elements identified throughout this document are intended to reinforce a culture of quality and trust within the pharmaceutical industry. Access Data Integrity Code of Conduct

Guidance: Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments

Pharmaceutical Inspection Convention/Pharmaceutical Inspection Co-Operation Scheme (PIC/S) – Good data management practices influence the integrity of all data generated and recorded by a manufacturer and these practices should ensure that data is accurate, complete and reliable. While the main focus of this document is in relation to data integrity expectations, the principles herein should also beconsidered in the wider context of good data management. Access PIC/S Guidance

Library of Data Quality, Records Management & FDA Recordkeeping Laws

Be compliant with US regulations and statutes on data integrity and recordkeeping in order to avoid stiff penalties and preserve corporate value. This robust collection of resources will prove to be quite helpful. Access Library


Evolution of Biopharmaceutical Control Strategy Through Continued Process Verification

Continued Process Verification Image

As defined in the ICH Q10 guideline, a control strategy is “a planned set of controls, derived from current product and process understanding, that assures process performance and product quality” (1). Every biopharmaceutical manufacturing process has an associated control strategy.

FDA’s 2011 guidance for process validation (2) describes process validation activities in three stages (Figure 1). A primary goal of stage 1 is to establish a strategy for process control that ensures a commercial process consistently produces acceptable quality products. Biopharmaceutical development culminates in the commercial control strategy, a comprehensive package including analytical and process controls and procedures. Stage 2 process performance qualification (PPQ) is needed to establish scientific evidence that a process is reproducible and will consistently deliver high-quality products. Stage 3 of validation and continued process verification (CPV) provides an opportunity to improve process control through the lifecycle of a product. Continue reading

SEE ALSO: 4 Steps for Managing Biopharmaceutical Manufacturing Projects

Response to the Publication of USP ‹1207›: Package Integrity Evaluation-Sterile Products

Container Closures

The BioPhorum Operation Group’s (BPOG’s) Container Closure Integrity Testing (CCIT) workstream would like to congratulate the United States Pharmacopeia’s committee for its latest revision to USP chapter <1207> Package Integrity Evaluation: Sterile Products. Generally, we believe it provides a comprehensive overview of the available methods for container–closure testing and outlines many important elements for consideration in establishing a successful CCIT strategy. We first responded to the USP <1207> draft when it was released for comment in 2014. And from our perspective, some of the changes that were proposed and concerns that were raised in 2014 clearly have been addressed. We are grateful to see that.

The purpose of this letter, however, is to highlight specific areas that cause us concern as a crossindustry group. We are aware that USP’s “informational” chapters are not compulsory. As end-users of such guidances, though — and as representatives of companies that receive the scrutiny of regulators — we recognize that informational chapters often evolve in practice to establish expectations. So any lack of clarity or any bias introduced toward specific methodologies is of concern. It is in this context that we would like USP to consider our further comments here.

These concerns center on the description, perception, and treatment of probabilistic and deterministic analytical methods — specifically dye and microbial ingress methods. We would like to see our concerns considered at the earliest possible opportunity, ideally precipitating an update to USP<1207>. Read article
SEE ALSO: 4 Steps for Managing Biopharmaceutical Projects

Therapeutic Gene Editing: An American Society of Gene & Cell Therapy White Paper

Gene Therapy Post image

Interested in learning more about gene editing and its therapeutic applications? Download a new white paper from the American Society of Gene & Cell Therapy (ASGCT). The document, titled “Therapeutic Gene Editing: An ASGCT
White Paper” is intended as background information for policymakers, patients, and the general public to help them Therapeutic Gene Editing - An American Society of Gene & Cell Therapy White Paperbetter understand gene therapy concepts and its related therapies.

The paper is designed to help people to better understand the ramifications of a soon to be released report on human gene editing by the National Academy of Sciences and National Academy of Medicine. This report, planned for release in early 2017, is expected to address the ethical, legal, and social implications of gene editing processes and suggestions for potentially needed policy.

Download White Paper

4 Steps for Managing the Criticality and Challenges of Biopharmaceutical Projects

Biopharmaceutial project management is a complex process. This SlideShare walks you through the process:

  • Challenges of biopharma project management
  • Scope of biopharmaceutical project management
  • Characteristics of great biopharmaceutical project managers – are we asking for unicorns?
  • 4 Steps for managing biopharmaceutical projects
    • Step # 1 – Clearly Establish Project Definition and Impacting Constraints
    • Step # 2 – Project Execution Planning
    • Step #3 – Project Execution
    • Step # 4 – Project Completion

Critical Steps for Outstanding Biopharmaceutical Project Management

Note: BioTechLogic is proud to be featured in the December 2016 issue of Pharmaceutical Manufacturing magazine.

Article in December issue of Pharmaceutical ManufacturingThe global biopharmaceutical market is expected to grow at a compound annual growth rate of 9.4 percent from 2014 to 2020, reaching $278 billion in revenue by the end of this six-year period. Growth is being driven by numerous factors, such as aging populations in most of the Western world and an increased prevalence of chronic disease. However, likely the most important contributor to growth is biopharmaceutical drugs’ superior effectiveness in treating many disease states, including treating conditions for which there were previously few effective drug treatment options available.

Given the growth of the biopharmaceutical segment, the industry needs to become increasingly better at managing biopharmaceutical projects in order for more treatment options to become available to patient populations. The objective of any project management pursuit is to complete the project on time, within budget, and within required quality or performance parameters. Given the complexity and intense regulatory demands of the pharmaceutical industry, project management is more difficult than many other segments. As if pharmaceutical projects weren’t demanding enough, biopharmaceutical project management is exceptionally challenging, requiring unique experience and expertise.

Biopharma project management challenges
Chemically synthesized drugs are typically better characterized by fairly established analytical technologies and techniques spanning the complete product lifecycle. Also, analytical techniques and manufacturing processes are typically more consistently repeatable, including at large commercial scale.

Biologics, on the other hand, have very complex production processes and are affected by a wide range of factors, including the cell system in which they are produced and inputs such as fermentation media and operating conditions. It is not easy to scale up biologics from laboratories with the quantities used for early analysis and pre-clinical testing to larger-scale batches, while maintaining product quality and batch-to-batch equivalence. Additionally, typically complex bioassays are required for batch release and stability assessment — testing that is usually more complex than the testing required for small molecule drugs.

Finally, because there is still a lot we don’t fully understand about the nature, characteristics and behaviors of living cells, outcomes are less predictable.  Continue reading article on page 27 of Pharmaceutical Manufacturing’s December 2016 digital issue

Top Pharmaceutical M&A Deals of 2016


Despite active M&A activity by conventional standards, 2016 was a fairly quiet year compared to 2015. The U.S. government cracked down on inversion-based deal making that drove so much of the mega M&A activity in 2015. For instance, Pfizer expected to save about $123 million in taxes after merging with Ireland-based Allergan. It would have been the largest merger in pharmaceutical industry history.

When the law changed, the Pfizer and Allergan deal immediately fell apart as did other inversion-based deals. Instead, 2016 M&A activity focused on strategically managing product portfolios and leading companies buying the innovation needed for growth.

What will 2017 hold? With the incoming Trump administration it is hard to tell. Cash repatriation policies mentioned during the campaign might bring a great deal of off-shore money back to the U.S. and spark another round of M&A mania.

The following is some of the most notable activity from 2016. Happy 2017!

Investor Acquired Deal(s) Description
Allergan plc, Ireland Anterios, Topokine Therapeutics, RetroSense Therapeutics, Vitae Pharmaceuticals, Akarna Therapeutics, Tobira Therapeutics, Chase Pharmaceuticals After the Pfizer merger deal fell apart in April 2016, Allergan made eight acquisitions and divested its generic drug business unit. These moves were designed to support their stated strategy of growing their branded drug strength. The deals totaled approximately $2.8B.
Shire plc, Ireland Baxalta, Inc., United States Shire completed its $32 billion merger with Baxalta with the goal of becoming the global market leader in rare diseases and other specialized disorders. Shire projected that the combined company would generate approximately 65% of its total annual revenues from rare disease products.
ViiV Healthcare, United Kingdom Bristol-Myers - HIV R&D portfolio, United States GSK’s global HIV business ViiV Healthcare acquired Bristol-Myers Squibb’s R&D HIV assets. The deal totaled $350M and reinforces GSK’s leadership in the HIV treatment arena.
Abbvie, United States Stemcentrx, Inc., United States Abbvie’s acquisition of Stemcentrx included Rova-T, a late-stage oncology drug. Rova-T is a novel biomarker-specific therapy that is derived from cancer stem cells and targets delta-like protein 3 (DLL3) that is expressed in more than 80 percent of SCLC patient tumors and is not present in healthy tissue. Rova-T has been submitted to the U.S. Food and Drug Administration for Breakthrough Therapy designation as it is under investigation as a third-line treatment in SCLC, where there is no currently approved therapy. This acquisition furthers Abbvie’s positon within the innovative oncology and specialty drug arenas. Stemcentrx was Abbvie’s one acquisition in 2016. The deal totaled $5.8B.
Gilead Sciences, Inc., United States Nimbus Apollo, Inc., United States Gilead Sciences acquired Nimbus Therapeutics’ Acetyl-CoA Carboxylase (ACC) Program for NASH and other liver diseases. The deal totaled $400M.
IMS Health Holdings, Inc., United States Quintiles Transnational Holdings, Inc., United States The merger with Quintiles was one of four deals IMS Health Holdings made in 2016. IMS Health Holdings continues to seek opportunities to strengthen its foothold in data analytics, data management and informatics. The deals totaled approximately $8.8B.
Pfizer, Inc., United States Anacor Pharmaceuticals, Bamboo Therapeutics, Medivation and AstraZeneca PLC, Small Molecule Anti-Infective Business Unit Rather than the inversion opportunity driven mega merger Pfizer hoped to close with Allergan in 2016, they made four acquisitions totaling about $21.3 billion. Each of the four deals strengthened Pfizer’s position in emerging treatment areas. For example, their acquisition of Anacor included a compound called crisaborole that represents great promise for the treatment of eczema – a large patient population. Could be blockbuster opportunity.
Teva Pharmaceutical Industries Ltd. - Generic Products, Israel Allergan plc, Ireland Teva Pharmaceutical Industries bought Allergan’s global generic business unit for approximately $38.8B. This acquisition should place it among the top ten pharmaceutical companies in the world.
Lonza Group AG, Switzerland Capsugel Belgium NV, Belgium The acquisition of Capsugel was one of three deals Lonza made in 2016. The deals totaled approximately $5.8B.
Baxter International, Inc., United States Claris Injectables Ltd., India Claris Injectables was Baxter’s one acquisition in 2016. The deal totaled $625M. Baxter is calling its acquisition of Claris Injectables “a foundational asset” as it seeks to become a global leader in the generic injectable pharmaceuticals market, which is estimated to be a $40 billion market and is growing at a 10% compound annual growth rate.
Asahi Glass Co., Ltd., Japan CMC Biologics A/S, Denmark Asahi Glass agreed to acquire 100 percent stake in CMC Biologics. CMC Biologics annual revenue was approximately $47M.
Sumitomo Dainippon Pharma Co. Ltd., Japan Tolero Pharmaceuticals, United States Sumitomo Dainippon Pharma Co. acquired Tolero Pharmaceuticals for approximately $780 million to reinforce their oncology drug pipeline.


  • Mergr
  • BioSpace
  • Pharma Letter
  • “Pharma Year in Review,” C&EN
  • “Baxter Buys Claris’ Generic Injectables Subsidiary for $625M,” GEN, December 15, 2016
  • “AbbVie to Expand Oncology Presence Through Acquisition of Stemcentrx and its Novel, Late-Stage Rova-T Compound for Small Cell Lung Cancer,” April 28, 2016, Abbvie press release
  • “Pharma M&A Market: Latest Challenges and Opportunities,” Peter Young, Pharmaceutical Executive, December 14, 2016
  • “Review of the year 2016: M&A,” George Underwood, Pharma Times, December 2016
  • “Trump’s corporate tax holiday could spur pharma M&A,” Carl O’Donnell, Reuters, December 6, 2016