Agreement to avoid ugly disagreements SDEA

 What is SDEA 

A service data exchange agreement (SDEA) is an agreement between two companies that ensures the roles and responsibilities of each company are clearly defined, especially related to the pharmacovigilance process. 

This agreement is necessary due to business requirements, such as pharmaceutical companies having to have partners in some countries instead of selling themselves or buying or selling their molecules to others. Often, an MAH may only be involved in distribution, marketing, or manufacturing. Knowing and defining who will do what in the PV process becomes essential in all such scenarios. This is also a requirement from regulatory agencies during audits or inspections.

 2. Types of SDEA 

As defined in the above image, there are various types of agreements. The most important and necessary one is between two MAHs. The SDEA can also have other supporting documents that may be used to define granular details, timelines, how to exchange information, etc. 

 3. When, who, and how do we write 

SDEA is written or drafted very early once the business agreements are signed. Usually, the pharmaceutical company with the global license or MAH initiates the SDEA. 

The SDEA should be finalized and signed before the first batch is in the market (worst case), but earlier is better. The safety database, SOP, Work instructions, and team readiness—in a nutshell, the PV system should be live and ready to onboard or delegate the product.

 4. Elements of SDEA

SDEA elements, as seen in the above image, are minimal basic requirements that must be defined. This is not an exhaustive list, and further granularity is required depending on the product, its risk minimization measures, local RA regulations, etc. Other factors that need to be addressed are BCP (Business Continuity Plan), Termination, confidentiality, etc.

 5. Challenges and Solutions

Challenges:

1. Data privacy can be challenging, especially if local laws vary.

2. Confidentiality policies may have differences that may be contradictory to SDEA terms

3. Meeting regulatory compliance requirements as per local laws and each company's policies

Solutions:

1. Regulatory adherence: Helps companies meet legal obligations at local laws. 

2. Efficient collaboration: Once roles and responsibilities are clearly defined, it helps meet local and global regulatory requirements.

3. Data quality:  Maintains safety data's accuracy, completeness, and timeliness.

4. Clarity: Confidentiality and data privacy should be clearly defined to avoid any inspection and audit findings.

Having SDEA is of utmost importance so that both companies and parties work and collaborate together. This will ensure that there are no ugly disagreements later.

Written by:

Dr.Shraddha Bhange.

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References:

Guideline on good pharmacovigilance practices (GVP) Module I – Pharmacovigilance systems and their quality systems (Europa. eu) 

Pharmacovigilance Agreements: Negotiating Safety Data Exchange Timelines: To Agree to Disagree? That is the Question | Therapeutic Innovation & Regulatory Science (springer.com) 

https://pvdrugsafety.com/2021/11/pharmacovigilance-agreements-pvas-and-safety-data-exchange-agreements-sdea/ 

Literature review in pharmacovigilance

1. Why is a literature review required:

A literature review for continuously monitoring the product's safety profile is a regulatory authority requirement across all countries. However, it goes beyond meeting compliance requirements as it helps MAH/Pharma companies utilize real-world data in various other documents, e.g., new indication applications, better understanding of the risks, and introducing or adjusting risk minimization measures as the safety profile changes. Literature serves as a source of information outside the company database. 

 2. Which databases are used for literature: 

The European Union has published a list of active substances (drugs) that need to be monitored in the literature. Other regulatory agencies may or may not have such an explicit list or name of drugs published; however, when a product has active PSUR, RMP, or any risk minimization measures, it becomes pertinent to have a literature review for those products. A literature review for identifying cases/ICSR is required for all products; hence, having one database for literature is mandatory. However, the industry standard is to have at least 2 databases, and whenever required, especially for MAH in European countries, local literature in the local language also becomes mandatory.

3. Literature search strategy:  Literature search strategy depends on three critical factors.

1. Phase of development of product and the status of the product

    A product that is an originator and still in a clinical development phase may require a class search or a search focused on toxicology, animal studies, etc., as the real-world data may be limited. However, for a generic product with a well-developed safety profile, the search will be limited to molecules and collecting natural clinical settings usage and patient outcomes.

The most common and required terms are adverse event, class and product terms, pregnancy and breastfeeding, and pregnancy outcomes.

2. Literature database 

This also drives the way we use search terms and the technical aspects, such as using the correct characters.

3. Local vs. Global Literature

The search strategy will also change based on local or global search. In the case of specific terms used locally in clinical publications, those will need to be targeted. 

4. Broad vs narrow search strategy

 The search strategy can be broad or narrow depending upon where the articles will be used and for what. When the risk is not established or not characterized, we usually use signal validation in the broad search. However, we use narrow when the risk is well known, and we want only certain aspects to be characterized, e.g., prevalence in specific populations. 

 4. Where are literature articles utilized 

The literature in PV is not limited to ICSR or signal management. It can be utilized for aggregate reports, e.g., PSUR, DSUR, etc. Additionally, for new indication applications, designing a study to determine which study safety outcomes and Benefit risk assessment.

 5. Points to consider for literature articles 

 5.1 ICSR

Validating an article as an ICSR from literature is the same as in any case: 4 minimum criteria. However, the same 4 minimum criteria must be relevant to the literature source. 

Product: Is your product available in this market/country? 

Is the literature article date or use of the product mentioned in the article after the product was launched in that country/market? 

Does the article mention the brand name or have the same composition as your product? 

We need to address these questions before adding this to the safety database.

Event: Add only events that occurred with company products or events after the company product was started. Add events that the author attributed to the company product.

Reporter and Patient: This criterion has no change per se except that patient identifiers must be available in the article. A table of patients with their age/gender, categorized into products they have taken or events that occurred. In a nutshell, we need to know that there were separate patients.

 5.2 Aggregate safety reporting

Articles that need to be included in the PBRER depend on multiple factors, e.g., sections in the PBRER, i.e., sections 9 or section 15, or 16. It also depends on the baseline safety profile of the product, what we know about the individual risk, and what outcome is expected from that section or risk. If it's a second PSUR, is there any particular request from PRAC? Generally, articles with large populations, varied/diverse patient populations that were not studied, specific outcomes, and changes in severity, seriousness, and frequency will be included. Articles that provide more information on the mechanistic action of drugs (previously unknown) or articles that provide new or relevant disease pathophysiology will also be included.

Written by:

Dr.Shraddha Bhange.

Connect with me Via comments below. (I do not respond to Facebook messages)

Support the cause of better rural education with me:ThinkSharp Foundation http://thinksharpfoundation.org/#home

References:

1. Detailed   guide regarding the monitoring of medical literature and the entry of relevant information into the EV database by the EMA (Europa. eu)

2. Welcome - Embase

3.MEDLINE   (nih.gov)

4. Allied    and Complementary Medicine Database (AMED) | EBSCO

Pharmacovigilance readiness for a Successful Product Launch

 Pharmacovigilance Readiness for a Successful Product Launch

Product launch is the most critical milestone for any pharmaceutical company and, consequently, even for vendors that support the company. As pharmacovigilance professionals, we may not know the extensive details from marketing and sales perspectives on how the launch is planned, but we do need to know more from regulatory and clinical perspectives and, of course, in detail about pharmacovigilance involvement in product launches.

As described in the figure below, there are different phases for the product launch, and these phases may usually take 1-2 years. Hence, the launch itself is usually planned 3-4 years ahead of the date the Pharma is planning to be in the market. 

Pharmacovigilance readiness starts as soon as the company decides to conduct a study for the product and to be its MAH. However, the clinical trials and post-marketing phases need to be aligned appropriately, as both requirements differ.

Which departments are involved in the launch 

The leading department or function is the marketing/brand function, which is usually comprised of leaders from all functions, i.e., medical affairs, clinical, regulatory, manufacturing, leadership, legal, finance, quality, and pharmacovigilance. 

Role of PV team 

 Launch readiness 

The PV team is a support team for this activity. Once the information is received from the launch team (the marketing team is the lead) the critical factors to consider are

1.  PV systems as per health authority requirements:

Standard operating procedures (SOP) for ICSR, AGGREGATE, SIGNAL. LITERATURE, SAFETY SYSTEMS ETC

Pharmacovigilance System Master File (PSMF) is ready

Product configurations in the Safety Database

Regulatory requirements are aligned in SOP, Database, and overall complaint

   

5. Literature set up:

The literature database is identified e.g. MEDLINE and Embase and if needed, another database

Global literature and Local literature in local language

Literature search strategy for product for ICSR and Aggregate. Literature search strategy for the PBRER section on risks.

6. Local country-specific requirements:

Suppose the product was approved without any studies or requirements fulfilled in local regions. In that case, local country-specific requirements from health authorities should be fulfilled at the time of local launch.

7.  RMP and risk minimization measures:

A risk minimization plan and measures (routine and additional) should be specified. Additional risk minimization measures like patient leaflets and healthcare professional cards have to be approved by the pharmacovigilance team at the time of launch and no later than that. This allows them to implement. If needed, the PV team needs to train the marketing and other functions involved in implementing education materials and additional measures.

8. Aggregate reports:

The schedule for aggregate reports (PBRER, DSUR, and PADER) should be finalized. The templates can be populated, and the strategy for presenting each section in this document, especially the safety strategy regarding risks, should be ready.

9. Signal management system - manual vs. database, which sources will be used (safety database, literature, EVDAS, FAERS), etc.- should be formalized and documented as part of the signal SOP or Signal plan at the product level if a function level does not exist or is different.

This is not an exhaustive list but a summary of critical requirements. Other requirements to be taken care of are training the PV team and other functions as required and creating an implementation plan with a dedicated project manager. 

 

 Written by:

Dr.Shraddha Bhange.

Connect with me Via the comments below. (I do not respond to Facebook messages)

Support the cause of better rural education with me: ThinkSharp Foundation http://thinksharpfoundation.org/#home

References :

1. Pharmacovigilance: Overview | European Medicines Agency (EMA) (europa.eu)

2.Smart Safety Surveillance (3S): Proven Approach to Building Functional LMIC Pharmacovigilance Systems (diaglobal.org) 

3. 2177-Successful-Biopharma-Product-Launch-v2.pdf (lek.com) 

Compliance in PV- MAH and Vendors

Compliance in Pharmacovigilance by 

Marketing Authorization holders and vendors

MAH needs to oversee its pharmacovigilance even if it has outsourced it to vendors. We all know this, but the implementation is critical.

The oversight starts with choosing the right vendors and ensuring checks and balances are in place. Vendors also need to have a robust and efficient partnership with their clients, going beyond just providing services to being partners. How do both achieve this synergistically?

Process level requirements:

1. An SOP should be in place at the QA level that describes the vendor selection process, selection criteria, and onboarding.
2. This SOP is at the company level and needs to be modified by the pharmacovigilance department/function. 
3. Mandatory audits along with the noted deficiencies and their corrective and preventive actions with timelines were conducted.
4. Quality monitoring metrics need to be in place for each activity that is outsourced e.g. ICSR quality metrics, PSUR quality checklist
5. The statement of work should be as clear as possible
6. Safety management plan- detailing for each activity (e.g., diagrams) how the ICSR workflow looks between MAH and vendor from receipt to submission. The same level of granularity is for aggregate reports from a kick to submission, signal detection, literature, HA requests, etc
7. Vendors must prepare client-specific documents, such as safety management plans, training presentations, QC checklists, and work instructions. 
8. Frequency of meetings and collaborations with various levels of team involvement, e.g., governance meetings with senior leadership, which can be quarterly, weekly meetings with the operational team, etc.
9. Monitoring plan that includes Key performance indicators that will be monitored, process, SOP, etc
10. Training requirements need to be fully discussed, and a training plan that will help frequent upgrades and awareness of vendor team on MAH's changing process needs to be in place
11. Team details (org chart, CV, JD) need to be made available at least for critical roles

Metrics and beyond for effective PV systems and functions

A vendor—MAH needs to be open, transparent, and honest with each other. Leadership plays a vital role here. Having frequent connections and dialogues helps immensely.

An MAH needs to understand and respect Vendors' opinions and suggestions. A vendor also needs to take a tailor-made approach when needed to meet MAH, where they have scientific justification for doing things according to their products.

Frequent training and workshops surely help build expertise on the vendor side that is imparted by MAH.

 

 Written by:

Dr.Shraddha Bhange.

Connect with me Via comments below. (I do not respond to Facebook messages)

Support the cause of better rural education with me:ThinkSharp Foundation http://thinksharpfoundation.org/#home