PJI Biotech 

PJI Biotech

  Strategic Quality and Regulatory Management Consulting


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China issues the rule of accepting overseas clinical trial data of drugs

Posted on October 26, 2018 at 12:45 AM Comments comments (0)
The China National Drug Administration issued the Guiding Technical Principles for the Acceptance of Overseas Clinical Trial Data of Drugs (Principles) on 10 July 2018, which standardize the rule of accepting the overseas clinical trial data of drugs. According to the Principles, overseas clinical trial data provided by applicants for drug registration in China shall be complete, correct, true and traceable. The process of obtaining the overseas clinical trial data shall comply with both the Good Clinical Practice of China and the ICH. The applicant shall submit comprehensive data concerning biopharmaceutics, clinical pharmacology, effectiveness and safety. After a review, the CNDA may choose to fully accept, partially accept or refuse to accept the submitted overseas data. Multi-national pharmaceutical companies will significantly benefit from these Principles, from the reduced cost of conducting clinical trials in China and the significantly reduced registration timeline.

Out of Specification (OOS) Results and Trending Program

Posted on October 26, 2018 at 12:45 AM Comments comments (0)
MHRA guidance for handling OOS results was recently updated and is available on MHRA website. FDA guidance for handling of OOS was initially issued in 1998 as draft and was finally issued in 2006. MHRA guidance on handling OOS results was initially published in 2013 and was updated to add handling of microbiological OOS. MHRA guidance is complementary to FDA guidance and provides flowcharts for OOS investigations. There are 3 phases of an OOS investigation. During Phase 1 and 2, investigation is performed to determine root cause of OOS in lab and manufacturing, respectively. During phase 3, a holistic assessment is performed to determine impact of OOS result on the impacted & other batches, stability etc. and to implement appropriate CAPA. There are two most common regulatory observations related to OOS. (1) Inadequate justification for invalidating tests and reoccurrence of invalid tests. (2) Inadequate and inconclusive investigation with no root cause and corrective actions. Invalid tests should be trended based on root cause to enhance assay robustness, procedures or training program, implement CAPA and to prevent reoccurrence of invalid tests. The potential or most probable root causes should be determined, where root cause cannot be determined and appropriate CAPA should be implemented for process improvements, as applicable. However, if there are numerous OOS for the same test where the root cause cannot be determined, then question arises if the specifications are adequate for the test. Is there a need to improve the process or the assay or the specification? Also, if there are numerous OOS for the different tests where root cause cannot be determined, then OOS investigation procedure and training on root cause investigation needs to be enhanced. Therefore, a good trending program for invalid tests and OOS test is very important to implement an effective CAPA and remediate OOS issues.

Brexit on Horizon

Posted on October 26, 2018 at 12:45 AM Comments comments (0)
We have been hearing about Brexit for quite some time. Brexit is impacting the life science industry in the UK and EU in several ways but mainly by causing regulatory uncertainty and patient access to medicine or supply chain impact. EMA issued a guidance on 24 November 2017, for market authorization holders to transfer current UK based market authorizations (MA) to different legal entity in EEA, which needs to be completed by March 2019. The MHRA position will be clear after further negotiations but there is a risk of Brexit disrupting the supply chain due to complexities caused by additional importation testing, batch certification and regulatory inspections. It has to be seen how negotiations will end but pharma companies need to be ready with Brexit strategies for supply chain management such as adding additional capacity for MA transfer, batch certifications and additional storage capacity to hold stock during the Brexit transition period.

Change Management

Posted on October 26, 2018 at 12:40 AM Comments comments (0)
Change Management is a critical quality system during the drug development and commercial phase of a pharmaceutical product. Post-approval changes are first categorized as minor, moderate and major based on product quality, product efficacy and patient safety risk. The second is risk-based categorization of regulatory communication as prior approval supplement (PAS) or notification. Any changes to established conditions (EC) in common technical document (CTD) necessitates submission to regulatory authority as PAS or notification. An effective change management system requires processes for science-based risk assessment and categorization of proposed change, approval by all impacted stakeholders, implementation as per approved protocol and post-implementation verification for unintended consequences, including the risk management if change is not implemented. Several regulatory guidance???s including recently published ICH Q12 Draft guidance, provides risk-based approach for implementation of post approval CMC changes.

Regulatory and Quality Intelligence

Posted on October 26, 2018 at 12:30 AM Comments comments (0)
An organization's ability to learn, and translate that learning into action rapidly, is the ultimate competitive advantage. Jack Welch There are 4 key attributes of successful compliant companies. 1. Rigorous internal audit program 2. Effective CAPA 3. Robust quality and regulatory intelligence system that provides knowledge needed to stay appraised of a dynamic regulatory environment 4. Commitment to act upon intelligence in timely manner. What is regulatory and quality intelligence? Regulatory information (oral or published) is the raw data used to create regulatory intelligence. Regulatory information can be internal (observations from internal and external audits) or external (guidance, regulations or regulatory trends). The data analysis, using data to create innovative strategies and integration into company corporate policies and procedures produces regulatory intelligence. Defining an effective regulatory intelligence system is critical. An effective regulatory intelligence system recognizes, tracks and ultimately predicted trends. There are 3 main step in any regulatory intelligence system, which are information gathering, information mining and transforming knowledge into actions. Regulatory intelligence helps timely and efficient product approval and maintenance. A good regulatory intelligence system ensures the continuous updates and improvement of existing quality systems based on evolving regulations and regulatory landscapes.

Data Integrity

Posted on February 7, 2018 at 11:35 AM Comments comments (0)
Regulators around the globe have issued guidances on data integrity in last five years (1-5). This is not something new. Guidances have been in place since drug development started. However, it has surfaced as a key issue in the last five years during regulatory inspections of raw materials and drug suppliers overseas. In simple terms, data (paper or electronic) should be complete, consistent and accurate throughout the data life cycle, i.e. from raw data generation and recording through use, migration, retention, archival and destruction. It is critical to ensure data integrity because data errors could make an adulterated drug batch reach the patient, thus impacting patient safety. What is the solution? The path forward includes 2 main steps: (A) Conduct a through assessment of current data integrity systems and identify if there are existing issues and remediate those issues. (B) Develop and implement sustainable data integrity systems by training employees and establishing the governance structure to provide oversight for management and continuous improvement of data integrity. (1) Data Integrity and Compliance with cGMP, Guidance for Industry (April 2016) https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM495891.pdf (2) MHRA GMP Data Integrity Definitions and Guidance for Industry (March 2015) https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/412735/Data_integrity_definitions_and_guidance_v2.pdf (3) WHO: Guidance on Good Data and Record Management Practices (September 2015) http://www.who.int/medicines/areas/quality_safety/quality_assurance/Guidance-on-good-data-management-practices_QAS15-624_16092015.pdf (4) PICS: Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments (August 2016) https://picscheme.org/en/publications. (5) CFDA Drug data management guidance (October 2016).

Brexit and Pharma Industry

Posted on February 6, 2018 at 7:50 AM Comments comments (0)
The United Kingdom decided to withdraw from the European Union on 23 June, 2016. The two-year process of leaving the EU on 29 March, 2019 was triggered on 29 March, 2017. Medicines and Healthcare Products Regulatory Agency (MHRA) issued an updated briefing to pharmaceutical companies in January 2018, indicating that current regulatory relationship remains unaffected. The UK will continue to be full member state until March 2019 and will fulfill its responsibilities as a member state until then. MHRA will continue to work closely with EMA in planning for the UK's withdrawal and will ensure minimum burden and sufficient implementation time for companies (1). On the other hand, EMA has mapped out the process for handling the Brexit related changes to alleviate some of the regulatory uncertainty for Pharma companies. On 24 November 2017, EMA issued guidance procedures related to Brexit (2) for medicinal products of human and veterinary use. This guidance indicates that as of 30 March 2019, the UK will become a third country. Market Authorization Holders (MAH) and applicants currently established in the UK need to ensure that necessary changes are made by 30 March, 2019. This means that MAH established in UK will have to transfer from the current UK-based MAH to a different legal entity established in the European Economic Area. This imposes significant burden on EMA and Pharma companies to complete and fully implement all transfers by 30 March, 2019. (1) https://www.gov.uk/government/news/mhra-update-to-pharmaceutical-companies-on-exit-preparations (2) http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/general/general_content_001707.jsp&mid=WC0b01ac0580a809a7

Mutual Recognition of Inspections between EU and US Authorities

Posted on January 22, 2018 at 9:35 AM Comments comments (1)
The European Union (EU) authorities and the Food and Drug Administration (FDA) signed the mutual recognition agreement (MRA) in February 2017, which enters into force on 01 November, 2017. The agreement is an annex to the EU-US MRA, which was signed in 1998 but is not yet implemented. This MRA will allow EU and US regulators to rely on each other GMP inspections and share inspection outcomes. Additionally, after transition phase, it will waive any requirements for importation batch release testing of products on entry into their territories. The aim of this MRA is to make better use of inspection capacity and reduce duplication. Update: In June 2017, the European Commission confirmed that the US FDA has the capability, capacity and procedures in place to carry out GMP inspections at a level equivalent to the EU. In October 2017, the FDA confirmed the capability of eight EU Member States (Austria, Croatia, France, Italy, Malta, Spain, Sweden, and the United Kingdom). Imported products still need to be batch tested until the FDA recognizes all EU member states' authorities for human pharmaceuticals. Products covered are human chemical pharmaceuticals, medicinal gases, human biologicals - including immunological and bio therapeutics - human radiopharmaceuticals, homeopathic medicines if classified as medicinal products, vitamins, minerals and herbal medicines if classified as medicinal products, active pharmaceutical ingredients and intermediate products and bulk pharmaceuticals. Products excluded are human blood and plasma, human tissue and organs, veterinary immunological and advanced therapy medicinal products. References: (1) http://www.ema.europa.eu/ema/index.jsp?curl=pages/home/general/general_content_000276.jsp&mid=WC0b01ac058005fa12 (2) https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm544357.htm

Emerging FDA Drug Inspection Trends in 2016

Posted on January 31, 2017 at 9:55 AM Comments comments (1)
Regulatory observations (483) over past years has forced quality executives to be on their toes. The top 5 key issues for 2016 are related to inadequate procedures and investigations, laboratory controls and aseptic processing. 1. Procedures not in writing and fully followed. 2. Lack of scientifically sound laboratory controls. 3. Thorough investigation of discrepancies and failures. 4. Absence of written procedures. 5. Deficient environmental monitoring system. How can these be prevented? Establishing a culture of quality is critical to prevent some of these issues. The mindset of companies should be not to start any task until SOP is effective and to always follow procedures. A robust training program on conducting investigations and aseptic processing as a new employee orientation is a must to ensure product quality and patient safety. Laboratory controls issues can be prevented with robust method development in R&D. Most of the time, all the required data is not collected during method development to support the investigations conducted during manufacturing, resulting into inadequate justifications. This should be followed by training, routine internal audits and standardization in quality laboratories, such as creating a guideline or standards for method validation, stability etc.