Coherence is the essence of everything successful. Then we add integrity.

December 2015

Life before the Yates Memorandum: DOJ False Claims Act statistics 1987-2015

15. december 2015 at 11:09 | Veronika Valdova, ARETE-ZOE |  Risk Management
False Claims Act statistics overview from October 1, 1987 to September 30, 2015 shows new matters, settlements and judgments and relator share awards as reported by the DOJ.

Let's see how the Yates memorandum (policy) from September 9, 2015 will affect FCA referrals.






















Data source:
Fraud statistics - overview. Civil Division, U.S. Department of Justice. October 1, 1987 - September 30 , 2015 (11/23/2015).
Fraud - All
  • ''New Matters'' refers to newly received referrals, investigations, and qui tam actions.
  • Non qui tam settlements and judgments do not include matters delegated to United States Attorneys' offices.
  • Relator share awards are calculated on the portion of the settlement or judgment attributable to the relator's claims, which may be less than the total settlement or judgment.
  • Relator share awards do not include amounts recovered in subsection (h) or other personal claims. See 31 U. S. C. § 3730(h).
DHHS
  • The information reported in these graphs covers matters in which the Department of Health and Human Services is the primary client agency.
DOD
  • The information reported in these graphs covers matters in which the Department of Defense is the primary client agency.

Cultural considerations: Good Distribution Practices in Russia

14. december 2015 at 8:00 | Veronika Valdova, ARETE-ZOE
Until recently, Russia was one of very few markets were Good Manufacturing Practice certificates were not part of Good Distribution Practices.

In 2013, Russia was still one of the emerging markets where pharmaceutical companies were lining up with investments. Russian pharmaceutical sector was, and still is, highly dependent on medicine imports.[i]

Almost 80% of drugs sold in Russian pharmacies are imported as medicinal products; the remaining 20% are manufactured from imported active pharmaceutical ingredients. Additionally, Russian government regulates the prices for essential 608 drugs. The lists differ from one region to another.[ii]

After the annexation of Crimea, undeclared invasion of Ukraine, and imposition of Western sanctions, Russian economy contracted substantially. Ruble devaluated steeply, and growing inflation undercut the purchasing power of Russians. Contrary to general perception, study conducted by Ernst &Young in late 2014 revealed that pharma executives do not see serious threats to their operations and investment plans in Russia and most of them have not been affected by the situation.[iii]

Russia, at that time a fast growing, emerging market with strong demand for investment, had its own rules for entry. The global pharmaceutical industry approached Russia with two distinct market strategies: they opted either for building local manufacturing capabilities or for partnership with domestic companies.[iv]

Apparent imbalance[v] of regulatory requirements for foreign producers as opposed to domestic, restrictions on interaction between healthcare workers and pharma representatives[vi], and lack of clear understanding of current legislation makes operations in the region difficult[vii]. According to the EY report, 77% of pharmaceutical companies in Russia struggle with excessive bureaucracy and corruption.[viii]

Russia is also a major market for counterfeit pharmaceuticals. Russia remains on the Priority Watch List in 2015 as a result of continued copyright infringement and trademark counterfeiting. The lack of enforcement of trademarks has resulted in the continued problem of counterfeit goods in Russia.[ix]

Russia accessed to the WTO in November 2011 and made commitments in the World Trade Organization Working Party Report to implement protections against "unauthorized disclosure of, or reliance on, undisclosed test or other data generated to obtain marketing approval for pharmaceutical products".[x]

Counterfeit pharmaceuticals manufactured in Russia are available through online pharmacies. In 2014 Russia's State Duma adopted new legislation aimed at criminalizing pharmaceutical counterfeiting as well as the distribution of fake and adulterated medicines. The new Federal Law "On amendment of the Federal Law On circulation of pharmaceuticals" No. 429-FZ was signed into law on 22 December 2014. This act introduced significant amendments into the existing law No. 61-FZ of 2010.[xi]



The amendment introduced new definitions, separated clinical trials from registrations; established new grounds for cancellation of registration; enacted good practices rules; established procedure for interchangeability of pharmaceuticals; imposed registration obligation an Marketing Authorization Holder; amended rules on pricing and reimbursement for essential and vitally important medicines; and established cease and desist order for illegal pharmacies.[xii]

New terms and definitions include biological medicinal products, immune-biological medicinal products, biotech medicinal products, gene-therapy medicinal products, orphan drugs, and homeopathic products.
The term "original medicine" was replaced with "reference medicinal product". This definition stands for a product, which has been registered in Russia for the first time, including generics. "Generic medicinal product" then refers to a drug that is biologically equivalent to "reference medicinal product".

The new law somewhat clarified powers of federal executive authorities and procedure for fast track procedure for "first three" medicines registered in Russia and for pediatric medicines.

The new act introduced procedure for determining interchangeability of medicinal products and, in particular, parameters for comparison. The requirement to demonstrate bioequivalence does not apply to reference medicinal products, herbal medicines, homoeopathic products and medicinal products, which have been approved in Russia for over 20 years.

State-authorized and financed Expert committee shall determine interchangeability of products registered before 1 July 2015. Applications for determining interchangeability shall be submitted by end of 2016. From January 2018 this information shall be included in Russian national Register of medicinal products.

Manufacturers and wholesalers shall comply with Good distribution practice and Good practices of storage and transportation as approved by authorized bodies.

The need to conform the manufacturing of medicines to the GMP (Good Manufacturing Practices) standards has been a mandatory licensing requirement in Russia since January 2014. In reality, however, this requirement has not worked properly. Russia does not yet have a formal procedure to confirm GMP compliance, and in the difference from other countries, it does not issue GMP certificates to compliant manufacturers. This made definition and detection of counterfeit and adulterated pharmaceuticals effectively impossible.



This has changed with the new law. After 1 July 2015, Russian Ministry of Public Health will be authorized to issue a GMP certificate based on the results of a manufacturing inspection by authorized experts.

Many of the new amendments must be specified by government decrees or orders of the Ministry of Healthcare and other authorities. The rules on Good manufacturing practice, Good distribution practices, and Good practices of storage and transportation of medicinal products, as well as good pharmacy practice are yet to be approved.[xiii]
Let's see if the dire situation in distribution of pharmaceuticals in Russia gets any better now.

[i] Patricia Van Arnum: Gauging the Potential of Russia's Pharmaceutical Market. DCAT Connect (May 27, 2014). Available at http://connect.dcat.org/blogs/patricia-van-arnum/2014/05/27/gauging-the-potential-of-russias-pharmaceutical-market#.vr6vzrpf8yc (accessed December 3, 2015)

[ii] Deloitte: Trends and practical aspects of development of the Russian pharmaceutical market - 2013. Available at: http://www2.deloitte.com/content/dam/Deloitte/ru/Documents/life-sciences-health-care/EN_Trends_and_practical_aspects_2013.pdf (accessed December 3, 2015).

[iii] EY: Russia's Pharmaceutical Industry: Setting a Course for Localization (October 2014). Available at: http://www.ey.com/RU/en/Issues/Business-environment/EY-russia-insights-october-2014 (accessed December 3, 2015).

[iv] Max Rubin and Julie Blackbeard: Putin - pharma's friend or foe in Russia? (October 29, 2013). Available at: http://www.pmlive.com/pharma_intelligence/putin_-_pharmas_friend_or_foe_in_russia_512893 (accessed December 3, 2015).

[v] Vladislav Shayman: Pharma 2020 and Import Substitution (October 8, 2014). Available at: http://www.themoscowtimes.com/guides/eng/pharmaceutical-business-health-care-2014/508482/pharma-2020-and-import-substitution-/508626.html (accessed December 3, 2015).

[vi] RG.ru: Федеральный закон Российской Федерации от 21 ноября 2011 г. N 323-ФЗ (November 23, 2011) Mhttp://www.rg.ru/2011/11/23/zdorovie-dok.html (accessed December 3, 2015).

[vii] EY: Pharmaceutical Industry in Russia Operation under the new conditions. Survey 2010 (2010). Available at http://www.ey.com/RU/en/Industries/Life-Sciences/Pharma-industry-survey-2010 (accessed December 3, 2015).

[viii] Michael Volkov: Challenges for Pharmaceutical Companies in Russia. Available at: http://blog.volkovlaw.com/2014/06/challenges-for-pharmaceutical-companies-in-russia/ (accessed December 3, 2015).

[ix] USTR: 2015 Special 301 Report. Available at: https://ustr.gov/sites/default/files/2015-Special-301-Report-FINAL.pdf (accessed December 3, 2015).

[x] WTO: Working Party on the Accession of the Russian Federation (2011). https://www.wto.org/english/thewto_e/acc_e/a1_russie_e.htm (accessed December 3, 2015).

[xi] PWC: Amendments to the Federal Law "On Circulation of Pharmaceuticals. (March 2015). Available at: https://www.pwc.ru/en/legal-services/news/assets/pharma_eng.pdf (accessed December 3, 2015).

[xii] Federal Law on Circulation of medicines of December 22, 2014 No. 429-FZ: Available at: acto-russia.org/files/zakon_ob_obr_ls_en.docx (accessed December 3, 2015).

[xiii] Vsevolod Tyupa: Russian Law on Circulation of Medicines - Significant amendments to come into force on 1 July 2015. Lexology (December 15, 2015). Available at: http://www.lexology.com/library/detail.aspx?g=710ebbe9-cca5-40eb-ba8b-e429d53b6c8f (accessed December 3, 2015).

Coffee in our new library

6. december 2015 at 18:06 | Veronika Valdova, ARETE-ZOE
Enjoy your cup of coffee and feel free to browse through selection of the most interesting materials produced for various projects in the last couple of years.

Library router:


Course Global Pharma Primer: The material included in these five modules serves many interests by facilitating understanding of construct, dynamics, and influences affecting regulatory policies and corporate decision-making that ultimately determine access, availability, and effectiveness of pharmaceutical products. We introduce and describe the highly specialized and often disconnected components of pharmaceutical research, drug development and manufacturing, marketing, regulatory policies and practices, and use case studies to qualify the relative effectiveness of safeguards to prevent harm. Additionally, how have pressures to reduce health care costs or increase safety actually affected both aspects of public concern within a global context because transnational interests influence national circumstances.


Survival guide to stem cell research and therapies: the course provides comprehensive guidance to publicly available resource materials, libraries and registries for people who are interested in understanding currently available treatment options involving human stem cells.


Big data in drug safety: The paper makes a case for change in the way data on safety of medicines is collected, structured, analyzed, visualized, and shared; moving away from the system of active reporting of individual case reports into national and international databases, toward collection and analysis of anonymous structured summary data from health care providers, in order to allow analysis of total numbers of treated patients and treatment outcomes; including adverse drug reactions and off-label drug use, to provide meaningful, population-based, statistically valid, bias-free, real-time information on safety and efficacy of products on the market without endangering patients' privacy. Such approach would significantly reduce privacy concerns and add value for stakeholders who are interested in timely and accurate information on benefit:risk profile of medicinal products.


Risk analysis primer: A variety of representative drug cases that have led to regulatory revisions will be template across the develop model to illustrate where signal detection could have been noticed that would have reduced patient casualty by providing an improvement in understanding to physicians prescribing medicines as an entry point for multidiscipline inclusion in process optimization and hazard reduction. Can drug development timelines be compressed while increasing regulatory confidence that public health interests and protections also advance?



Risk management plan (RMP) for opioid therapy: Prescription opioids cause more deaths than all illicit drugs combined. Law enforcement focus is on strict control of Rx and preventing diversion. This RMP focuses on frequent control of therapeutic range (TR). Frequent TR checking is possible if there is high capacity equipment with high sensitivity and specificity. Minimization of sample preparation time reduces labor time and overall cost.


Book Medicines for Women by Mira Woolrych-Harrison to which I contributed by co-authoring chapter "Political and religious perspectives on managing the risks and benefits of women's medicines," with review of the chapter by Frank Wallace, MD (Avatar Worldlink).



Paper "The human rights responsibilities of multinational pharmaceutical firms in host nation states" published in Journal of the International Relations and Affairs Group in June 2012 analyses the responsibilities of global pharmaceutical industry when conducting research in developing economies.


Article "The dangers of outsourcing personal medical data of PTSD patients" (Monitor SIRS, 2012) analyzes the risks associated with uncontrolled outsourcing of processing of medical data of PTSD patients.


Boyd cycle in clinical research and drug safety: To make any system oriented toward desired outcome, systems approach is necessary to make the feedback mechanism work. Boyd's OODA loop is an elegantly simple grand theory, which contains high quality insight into strategic essentials. OODA loop has extensive domain of applicability, including clinical research and post-market drug surveillance.


Lessons from big industrial accidents and their relevance for the pharma industry, as presented at the 4th World Congress of Clinical Safety, Vienna (2015) organized by International Association of Risk Management in Medicine (IARMM).


Systems Theoretic Accident Model and Processes (STAMP) can be utilized in pharmaceutical industry in multiple different ways to define safe range of operation, impose constraints and enforce them by design and operations.


Course on Good distribution practice and supply chain security is currently under preparation. It will cover introduction into the regulatory environment in the U.S., EU, Japan, China, India and Russia, review case studies and enforcement actions in the area of product tampering and counterfeiting, and explain the impact of globalization and consolidation on supply chain security.


Resource guide relating to the 1080 scare in New Zealand: In November 2014 dairy giant Fonterra and national lobby group Federated Farmers received anonymous threatening to put 1080 poison in infant formula unless the government banned the agricultural pesticide by the end of March. In early March, the New Zealand police held a press conference, in which they appealed to the public for information regarding the threats. Environmental terrorism was widely discussed as the underlying motive. In October 2015, the case took a surprising turn, when local businessman was charged with criminal blackmail.


Current Good Tissue Practice (CGTP) governs the methods used in, and the facilities and controls used for, the manufacture of human cells and tissue based products (HCT/Ps) including all steps in recovery, donor screening, donor testing, processing, storage, labeling, packaging, and distribution. (21 CFR 1271: CGTP).


Application of risk, issue and opportunity management in drug development: the presentation covers establishing an effective risk management process, risk management, relation to other risk management systems, issue management, opportunity management and management of cross-program risks. Special attention is paid to alignment of risk management programs between stakeholders in clinical research, specifically the sponsor, investigator, and IRB/EC.


Book Dark Side of a Mountain is a historical study of the effects of ideology, religion and culture on medical science. Section The Code is dedicated to The Book of Leviticus and its 12th century annotation by Moses Maimonides. The root cause of the 1348 plague was flawed life-science doctrine which could not be challenged due to ideological and religious terror. Section Medical Oaths presents different concepts in medical ethics around the globe. Japanese medical ethics gets special attention, due to unique relationship between martial arts and the art of medicine. Eugenic Trail deals with the topic of pedigree, hereditary entitlement and inbreeding, and search for the causes of societal evils. Eugenics transformed from science to ideology in the mid-19th and early 20th century, but only in Nazi Germany it took on its most malignant form. Whilst the American version was driven by quest for hereditary causes of crime, harlotry, and pauperism, European cousins were pushing a case for the indispensability of noble families out of fear of spread of French troubles (the Revolution of 1848) to surrounding monarchies.


About 90% of all risk management efforts within the industry concentrate on regulatory compliance. Here is an overview of EU regulations in pharmacovigilance.


Diabetes drug Avandia (Rosiglitazone, GSK) was a promising medication and a top-seller until 2007, when its cardiovascular side effects and FDA's role in evaluation of its safety came under intense public scrutiny. Avandia triggered discussion on FDA's role in evaluation of safety of Avandia, and other medicines, and the need for reform in post-market surveillance. STAMP case study utilized research and materials produced during coursework on Life-Cycle Strategic Plan for the same drug.


Reliance of authorities on insider information requires adequate protections offered to whistleblowers, i.e. counseling, financial and legal aid, re-qualification, resettlement and/or a witness protection programs. Risk to whistleblowers is difficult to assess because of unavailability and inaccessibility of relevant data. Little information is available on the outcomes of whistleblower suits in federal/state courts. Obtaining data directly from state courts' systems would require review all tort filings - a prohibitively expensive and time-consuming process.


Area study on Ukraine from June 2015 (resource guide):


Research: Czechoslovakian hospital in North Korea during the Korean War and Activities of Czechoslovakian scientists in the 1950s. Material for this research was collected in 2012 in the Military Historical Archive in Prague and includes wide range of documents mainly from the funds of Ministry of National Defense from the early 1950's.


That's it for now, enjoy your coffee!