mardi 18 décembre 2018

Communication de Scott Gottlieb FDA Commissioner

Statement from FDA Commissioner Scott Gottlieb, M.D., on the agency’s efforts to improve drug quality through vigilant oversight of data integrity and good manufacturing practice


Ensuring the safety of our nation’s drug supply is a cornerstone of our consumer protection mission. Overseeing the quality and safety of pharmaceutical manufacturing is key to these efforts. With the emergence of new markets, supply chains are more complex. Drug production and testing operations have also become more computerized. These changes represent new opportunities and challenges.
Having clear guidelines for companies on how to prevent product quality issues is an important step to protecting patient safety and preventing drug shortages of critical medicines. To meet these challenges, our policies and guidance must also evolve to ensure that quality standards are maintained, and to assist companies in building a culture of quality. To that end, one area we’ve focused new attention on in recent years is data integrity. Our goal is to ensure that the data associated with drug manufacturing are complete, consistent, and accurate, and therefore reliable.
Over the past decade, we’ve uncovered situations in which drug quality data and information are not accurate. This can mask problems and failures. Sometimes, data integrity concerns are a result of deceptive practices. But more commonly, they’re a result of inadequate processes and systems to ensure reliable and accurate data. In all cases, we regard any lapse in data integrity as a risk to patient safety. Patients can’t be assured of the safety and effectiveness of their medication when data has been altered.
In recent years, the FDA has focused additional resources on efforts to prevent, uncover and combat data integrity lapses. We’ve focused new efforts on these risks, and to train our staff on identifying concerns related to data integrity. Today, we’re building on these policies by updating our guidance for industry on ensuring data integrity and compliance with current good manufacturing practice (CGMP).
One critical way to help ensure product quality is to prevent data integrity lapses in the first place. That’s why we’ve worked to provide industry with clear guidance, so manufacturers have the tools and systems in place to prevent adulterated products from entering the U.S. marketplace. Companies need to create a quality culture where employees understand the seriousness of data integrity and promote data integrity as a core value. A work environment where employees are encouraged to promptly identify and properly report data issues is essential to product safety.
This new guidance is one part of our multi-layered approach to ensuring the integrity of data. We also use inspections to uncover data integrity problems. For example, our pre-approval inspection process is used to help ensure the integrity of data by evaluating, among other factors, its proper storage and handling. In tandem with pre-approval inspections, we also conduct thorough assessments of applications prior to approval and when companies submit information about changes to their manufacturing processes.
These are just some of the steps we take as part of a comprehensive approach to ensuring data integrity.
As the industry has globalized, we’ve expanded our partnerships with our international regulatory counterparts. This allows us to regularly exchange information about quality and data integrity related violations if they’re observed in facilities around the world. We also communicate regularly with the global industry participants to advance best pratices on data security to help manufacturers advance their own compliance policies.
Our new guidance document is aimed at promoting these efforts.
This new guidance, Data Integrity and Compliance With Drug CGMP: Questions and Answers is an update to our 2016 draft guidance. The guidance covers the design, operation, and monitoring of systems and controls to maintain data integrity. The agency revised the guidance in response to public comments requesting additional details on our thinking on current best practices. The revised recommendations are aimed at helping manufacturers address identified data integrity lapses, implement best practices to address gaps that can create risks to data integrity, and ensure consistent awareness and commitment to ensuring data integrity. The principles are relevant to manufacturing employees and management.
We continue to observe CGMP violations involving data integrity, which underscore the need to provide industry with guidance and address observed problems. When we see these violations, we take appropriate enforcement actions against manufacturers. We also expect all manufacturers to conduct timely and appropriate investigations of suspected problems, including expanding the scope beyond the narrow problem first observed into any other potentially impacted data, batches, or products. Pharmaceutical quality can only be assured by robust quality control, which includes vigilant oversight of data integrity.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
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Plus d'information ici 

mercredi 21 février 2018

La "data integrity" dans les laboratoires de contrôle non pharmaceutiques

Un exemple médiatisé des pratiques de "retest into compliance" dans l'industrie agro-alimentaire.

Plus d'information ici.

mercredi 31 janvier 2018

L'utilisation des données de sérialisation

Michele D'Alessandro, Vice President and CIO, Manufacturing IT at Merck & Co., Inc. partage des conseils sur la façon dont les données de sérialisation peuvent être utilisées, quels défis doivent être surmontés et les applications pratiques : Big data, apprentissage automatique et intelligence artificielle sont au programme.

Plus d'information ici et .

mercredi 3 janvier 2018

La "blockchain" et ses applications possibles dans l'industrie pharmaceutique

Cet article intéressant fait le point sur l'utilisation possible de la technologie "blockchain" dans les études cliniques... A quand l'utilisation en distribution du médicament ?

Plus d'information ici.

dimanche 3 décembre 2017

Un article intéressant sur la "Data Integrity" dans les analyses microbiologiques

Cet article fait le point sur les risques d'intégrité des données dans les méthodes d'analyse microbiologiques classiques et alternatives ; sur le critère d'"accuracy", les auteurs suggèrent notamment que la vérification par un deuxième opérateur soit limitée aux résultats en dehors des limites d'alerte et/ou d'action, hors spécification (OOS) ou ambigus.

Plus d'information ici.

jeudi 2 novembre 2017

La reconnaissance mutuelle des inspections des fabricants de médicaments entre l'UE et les États-Unis entre en phase opérationnelle

L'agence américaine a déterminé qu'elle reconnaîtrait huit autorités européennes de réglementation des médicaments capables d'effectuer des inspections dans des installations de fabrication répondant aux exigences de la FDA. 

Cela signifie que l'ARM UE-USA peut commencer, pour ces 8 pays, le 1er novembre comme prévu. 

Les huit autorités réglementaires de l'UE initialement reconnues comme compétentes sont celles situées en Autriche, en Croatie, en France, en Italie, à Malte, en Espagne, en Suède et au Royaume-Uni.

Plus d'information ici.

jeudi 31 août 2017

L'EMA et l'US FDA signent un accord de confidentialité

La Food and Drug Administration américaine peut maintenant partager des informations non publiques et commercialement confidentielles, y compris les secrets commerciaux relatifs aux inspections des médicaments, avec les régulateurs de l'UE après que les parties aient signé un nouvel engagement.

L'engagement de confidentialité, signé par la FDA, l'Agence européenne du médicament et la Commission européenne, est «une étape importante dans la mise en œuvre continue de la reconnaissance mutuelle des inspections des fabricants de médicaments» et vise à renforcer les liens entre l'UE et les États-Unis, selon L'EMA.

"En fin de compte, cela contribuera à une utilisation plus efficace des ressources d'inspection par les organismes de réglementation pour la protection de la santé humaine et animale", a-t-il noté.


Les accords de confidentialité transatlantique, permettant l'échange d'informations confidentielles dans le cadre de processus réglementaires et scientifiques, sont en place depuis 2003, mais un échange complet de données, y compris des rapports d'inspection complets, n'a pas été possible jusqu'à présent.

Le nouvel engagement permettra aux régulateurs de prendre des décisions en fonction des résultats des rapports d'inspection de chacun et d'utiliser davantage leurs ressources d'inspection pour se concentrer sur les sites de fabrication à haut risque.

Source Pharmatimes

mercredi 2 août 2017

L'ANSM sanctionne un fabricant chinois

Ce rapport de non conformité de l'ANSM publié sur le site EUDRAGMDP mentionne plusieurs écarts critiques et majeurs liés à la Data Integrity :
Nature of non-compliance : Overall around 22 deficiencies were observed, out of which one was classified as critical and three as major // Critical: manipulation, backdating and falsification of GMP documents such as batch manufacturing record, report of starting material manufacturer audit, GC and HPLC chromatograms. // Major 1: undeclared workshop without any traceability of the activities underaken. // Major 2: undeclared storage of unidentified product without any traceability. // Major 3: poor standards for issuance of batch manufacturing records.
Plus d'information ici.

mercredi 26 juillet 2017

US FDA et Cloud Computing

Cette ligne directrice de la FDA donne des recommandations intéressantes sur l'utilisation des enregistrements et signatures électroniques dans les études cliniques et plus particulièrement sur l'utilisation des services applicatifs dans le Cloud : 

B. Outsourced Electronic Services 
FDA recognizes that sponsors and other regulated entities may choose to outsource electronic services. Examples of these types of electronic services are data management services, including cloud computing services. According to the National Institute of Standards and Technology, cloud computing is defined as “a model for enabling ubiquitous, convenient, on-demand network access to a shared pool of configurable computing resources (e.g., networks, servers, storage, applications, services) that can be rapidly provisioned and released with minimal management effort or service provider interaction.” 
When these electronic services are used to process data for FDA-regulated clinical investigations, sponsors and other regulated entities should consider whether there are adequate controls in place to ensure the reliability and confidentiality of the data. Sponsors and other regulated entities should consider the factors in the following bulleted list when determining the suitability of the outsourced electronic services. If the outsourced electronic service does not provide the data security safeguards described in the following bulleted list, sponsors and other regulated entities should consider the risks of using such service (e.g., infringement of patient privacy rights, lack of reliability of the data in the clinical investigation and its regulatory implications).
  • Validation documentation (see sections IV.A.Q1 and IV.B.Q15)
  • Ability to generate accurate and complete copies of records
  • Availability and retention of records for FDA inspection for as long as the records are required by applicable regulations
  • Archiving capabilities
  • Access controls (see section IV.A.Q4) and authorization checks for users’ actions
  • Secure, computer-generated, time-stamped audit trails of users’ actions and changes to data
  • Encryption of data at rest and in transit
  • Electronic signature controls (see section V)
  • Performance record of the electronic service vendor and the electronic service provided
  • Ability to monitor the electronic service vendor’s compliance with electronic service security and the data integrity controls

Plus d'information ici.



mercredi 28 juin 2017

L' US FDA publie une ligne directrice Q&A sur le 21 CFR Part 11

Cette ligne directrice s'applique plus particulièrement aux études cliniques et comprend 28 questions et réponses qui traitent, entre autres, de ce qui suit:

  • Les procédures qui peuvent être suivies pour s'assurer que les enregistrements électroniques et les signatures électroniques répondent aux exigences de la FDA et que les enregistrements et signatures puissent être considérés comme fiables, et généralement équivalents aux enregistrements et aux signatures manuscrites exécutées sur papier,
  • L'utilisation de l'approche fondée sur le risque lors de la validation de systèmes électroniques, la mise en place de pistes de vérification pour les enregistrements électroniques et les enregistrements d'archives qui sont pertinents pour les recherches cliniques.

Le document Q & A vise à encourager et à faciliter l'utilisation de dossiers et de systèmes électroniques pour améliorer la qualité et l'efficacité des études cliniques. Il est destiné aux sponsors, aux chercheurs cliniques, aux comités d'examen institutionnels et aux organismes de recherche sous contrat (CRO).

Il est disponible ici.

lundi 26 juin 2017

Carton plein pour ce fabricant d'API chinois

Cette injonction de l'US FDA ne contient que des écarts liés à la Data Integrity :

1.    Failure to prevent unauthorized access or changes to data, and failure to provide adequate controls to prevent omission of data.
 
Our inspection found your laboratory systems lacked controls to prevent deletion of and alterations to electronic raw data.
 
a.    Our review of audit trail data revealed that your analysts manipulated the date/time settings on your high performance liquid chromatography (HPLC) systems. During the inspection your analysts admitted to setting the clock back and repeating analyses for undocumented reasons. Initial sample results were overwritten or deleted, and unavailable for our investigators’ review. Your firm reported only the passing results from repeat analyses.  When test results are overwritten, the quality unit is presented with incomplete and inaccurate information about the quality of the drugs produced by your firm.
 
b.    Your quality control analysts used a shared login account to access HPLC systems. This shared account allowed analysts, without traceability, to change the date/time settings of the computer, to modify file names, and to delete original HPLC data.
 
c.    Seven out of (b)(4) of your firm’s HPLC systems used for API testing had the audit trail feature disabled, although all (b)(4) had audit trail functionality....
 
2.    Failure to maintain complete data derived from all laboratory tests conducted to ensure compliance with established specifications and standards.
 
Our investigators found that you failed to maintain complete data for all laboratory analyses, and you relied on incomplete information to determine whether your drugs met established specifications.
 
a.    HPLC chromatograms were deleted and not available for our investigators’ review. In your response, you acknowledged that in January 2016, “some data was deleted” while the network edition of the chromatographic operating system software was installed.
 
b.    Our investigators found a recurring practice of re-testing samples until acceptable results were obtained. For example, our investigators found repeat HPLC testing for related substances of crude (b)(4), batch (b)(4). The initial test displayed an unknown peak in the chromatogram. A different analyst retested the batch five days later: this analysis did not display the unknown peak. Only the results of the second analysis were used for batch disposition, without documented justification or investigation...

3.    Failure of your quality unit to exercise its responsibility to ensure the API manufactured at your facility are in compliance with CGMP, and meet established specifications for quality and purity.
 
Our investigators found batch production records that contained blank or partially completed manufacturing data and lacked dates and signatures for verification. For example, in your (b)(4) plant, our investigators found a batch record for (b)(4) starting material, batch (b)(4), with sticky notes from the quality assurance department directing operators to enter manufacturing data, such as missing weight and volume entries. Also, your quality unit did not approve this batch record before the material was used in further manufacturing.
 
All data in CGMP records must be complete and reliable so it can be evaluated by the quality unit during its batch review, as well as maintained for additional CGMP purposes.
 
Other documents—including cleaning records and equipment use logs—were also found to be partially completed, without dates and signatures for verification, or with pages or spaces intentionally left blank for documentation at a later time.
 
Your quality unit was aware of these unacceptable production department practices but did not ensure they were corrected.

Plus d'information ici.

lundi 29 mai 2017

Des manquements importants pour ce fabricant chinois

Ce fabricant chinois a reçu une injonction sévère des autorités américaines dont certaines sont liées à l'intégrité des données :

3.    Failure to have laboratory control records that include complete data derived from all laboratory tests conducted to ensure compliance with established specifications and standards.
For example, our investigator reviewed the audit trail from your assay testing for (b)(4) lot (b)(4), and found that you tested the same sample set three times over several days without documentation or investigation. You reported only the result of the third and final test for purposes of completing your certificate of analysis and releasing this batch of API.
4.    Failure to prepare adequate batch production records and record the activities at the time they are performed.
For example, our investigator found that your operator used process parameter values from previous batches of (b)(4) to complete new batch records when she was too tired to immediately record the data and had forgotten the values.          

Plus d'information ici.



lundi 15 mai 2017

La disponibilité des enregistrements électroniques citée dans cette injonction

L'agence américaine mentionne l'incapacité de cette société indienne à fournir des enregistrements électroniques à des fins d'inspection :

3.      Failure to provide records required to be readily available for authorized inspection (21 CFR 211.180(c)).
 
During the inspection on October 18, 2016, your firm did not provide batch records to our investigator. At the conclusion of the inspection, you stated that you would provide these records electronically within a matter of days. To date, FDA has not received any batch records.

Plus d'information ici .


Ne manquez pas l'événement A3P du GIC eCompliance sur la Data Integrity le 20 juin prochain à Lyon ; plus d'information ici.