What are skills required to review documents

The key skills required to effectively review documents are:

1. **Analytical skills** to identify errors, inconsistencies, and gaps in information, and evaluate the importance and validity of documents[1][3].

2. **Attention to detail** to check for spelling, grammar, punctuation, formatting, and style errors, as well as factual or logical errors[1][2]. 

3. **Communication skills** to write clear, concise, and professional reports summarizing document review results, and convey findings to team members and stakeholders[1][2].

4. **Technical skills** to use document management systems, databases, search engines, and e-discovery software like Relativity, Ringtail, and Concordance[4].

5. **Critical thinking skills** to identify biases, assess credibility, compare arguments, and synthesize information from multiple documents[1].

6. **Ethical skills** to maintain confidentiality, privacy and security, and avoid conflicts of interest when reviewing sensitive information[1].

7. **Editing and writing skills** to review and summarize complex legal documentation[2].

8. **Organizational skills** to manage large volumes of information and documents[4].

Proficiency in specific document types like mortgages, loans, and foreclosure documents is also beneficial for document reviewers[4].

Citations:

[1] How to Master Document Review Skills and Competencies - LinkedIn https://www.linkedin.com/advice/3/what-skills-competencies-required-effective-1f

[2] How to Become a Document Reviewer (Plus Duties and Skills) https://ca.indeed.com/career-advice/finding-a-job/document-reviewer

[3] Document Reviewer Skills and Essential Traits - LiveAbout https://www.liveabout.com/top-document-review-skills-2164651

[4] 15 Document Reviewer Skills For Your Resume - Zippia https://www.zippia.com/document-reviewer-jobs/skills/

[5] Document Review Specialist Must-Have Skills List & Keywords ... https://www.ziprecruiter.co.uk

Difference between review and verification

The difference between review and verification lies in their purposes and methodologies:

- **Review** involves evaluating the suitability, adequacy, or effectiveness of an object to achieve established objectives. It is a process of determining whether the design or product meets the required standards. Reviews can occur throughout the design phase and at key milestones in the development process. Examples include management reviews, design and development reviews, and peer reviews[4].

- **Verification** ensures that specified requirements have been fulfilled by providing objective evidence. This can involve inspections, testing, reviewing documents, and performing alternative calculations. Verification occurs after the completion of development stages, prior to validation, to confirm that the product meets all specified design and requirement specifications[4].

In summary, review evaluates the design's ability to meet objectives, while verification confirms that the product meets specified requirements through objective evidence.

Does reviewer should be subject matter expert

A reviewer should be a subject matter expert in the specific domain or topic being reviewed. The key differences between a reviewer and a subject matter expert are:

- **Subject Matter Expertise**: A subject matter expert (SME) has deep, specialized knowledge and experience in the particular field or topic. They are considered authorities in that domain.

- **Review Role**: A reviewer, who may also be an SME, is responsible for evaluating the content, accuracy, and effectiveness of a product, process, or document against defined requirements or standards. The reviewer provides feedback and recommendations.

The main reasons why a reviewer should be a subject matter expert:

1. **Relevant Expertise**: An SME can provide informed, credible feedback based on their extensive knowledge of the subject area. This ensures the review is thorough and meaningful.

2. **Identification of Issues**: An SME can more readily identify technical inaccuracies, gaps, or problems that a non-expert may miss.

3. **Valuable Insights**: SMEs can offer strategic insights, best practices, and recommendations that improve the final product or process.

4. **Credibility**: Having an SME conduct the review lends greater credibility to the review process and its outcomes.

5. **Efficiency**: An SME can complete the review more efficiently since they already possess the necessary domain knowledge.

In summary, utilizing subject matter experts as reviewers is critical to ensuring the quality, accuracy, and effectiveness of the work being reviewed. Their specialized expertise is invaluable in identifying issues and providing meaningful feedback.

Role of verification in report review

The role of verification in report review is to confirm that the information presented in the report is accurate, complete, and meets the specified requirements. Some key aspects of the role of verification in report review include:

1. Confirming Accuracy: Verification ensures that the data, calculations, and conclusions in the report are factually correct and free of errors. This involves checking source data, re-performing analyses, and validating the logic and reasoning.

2. Validating Completeness: Verification checks that the report covers all the necessary information and addresses all the required elements as per the defined scope and objectives. This helps identify any gaps or missing components.

3. Ensuring Compliance: Verification confirms that the report adheres to relevant standards, guidelines, and organizational policies. This includes checking formatting, structure, and adherence to reporting requirements.

4. Identifying Improvements: The verification process can uncover opportunities to enhance the quality, clarity, and effectiveness of the report. Reviewers can provide feedback and recommendations for improvement.

5. Establishing Credibility: A thorough verification process lends greater credibility to the report's findings and conclusions, as it demonstrates the rigor and attention to detail applied.

6. Mitigating Risks: Verification helps catch and address any issues or discrepancies before the report is finalized and distributed, reducing the risk of errors, omissions, or misinterpretations.

In summary, the role of verification in report review is to ensure the accuracy, completeness, and compliance of the information presented, thereby enhancing the overall quality, reliability, and usefulness of the report.

difference between verification and review

The key differences between verification and review are:

1. Purpose:

   - Verification ensures that the product or information meets the specified requirements and is correct.

   - Review evaluates the suitability, adequacy, or effectiveness of a product or process to achieve established objectives.

2. Methodology:

   - Verification involves inspections, testing, document reviews, and alternative calculations to provide objective evidence.

   - Review is a more subjective process of evaluating design, content, and performance against standards.

3. Timing:

   - Verification occurs after development, prior to validation, to confirm the product meets requirements.

   - Review can happen throughout the design and development process at key milestones.

4. Expertise:

   - Verification is typically conducted by subject matter experts who have deep knowledge of the domain.

   - Reviewers may or may not be subject matter experts, but they provide an objective evaluation.

5. Outcome:

   - Verification confirms that the product is "built right" according to specifications.

   - Review determines if the "right product" is being built to meet user needs and objectives.

In summary, verification is focused on confirming correctness, while review is focused on evaluating suitability and effectiveness. Both play crucial and complementary roles in ensuring high-quality products and processes.

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Drug shortage Supply Chain Risk Assessment by EMA

On 18th of June 2024, the EMA has issued templates for Shortage Prevention Plans (SPPs) and Shortage Mitigation Plans (SMPs). Marketing authorization holders (MAHs) in the European Union/European Economic Area are encouraged to create Shortage Prevention Plans to minimize the risk of medicinal shortages.

The availability of medicinal products is a central point in the strategy of the European Medicines Agency Network until 2025 and the European Commission's pharmaceutical strategy, which led to the revision of the pharmaceutical legislation in April 2023. The draft regulation obliges MAHs to establish Shortage Prevention Plans and Shortage Mitigation Plans.

In times of crisis, in form of a public health emergency or a major event, SPPs are already obligatory under Regulation 2022/123, for drugs listed in the list of critical medicines for that particular crisis.

The extent of the documents should correspond to the risk level of the medicine. For this reason, the ICH Q9 guideline on quality risk management is to be applied.

Companies are recommended to involve their highest level of management in the development of SMPs/SPPs. The plans should be created in English and, if necessary, translated into the local language upon request of the national competent authorities. As part of the pharmaceutical quality system, SPPs should be regularly updated and evaluated.

Shortage Prevention Plans help to identify and manage potential risks in the supply chain and include information on the MAH, the supply and manufacturing chain, key data on stock, sales, consumption and manufacturing and an analysis of the history of supply issues. A SPP should be in place for each medicinal product marketed by the MAH. The minimum requirements for the SPP state that MAHs should analyze and evaluate weaknesses in the supply chain. The robustness of shortage prevention measures is to be evaluated. MAHS are obliged to assess the risks of supply interruptions for patients. A medicine shortage risk register should be developed to identify clinically significant products based on therapeutic use and availability of substitutes. Using available information such as root cause analysis of shortages, the MAH is required to determine whether corrective and preventive actions or revalidation are needed, both nationally and internationally. Furthermore, MAHs should ensure that minimum stock levels are maintained at national levels. Measures to prevent drug shortages should be reviewed regularly.

Shortage Mitigation Plans are designed to eliminate potential or actual drug shortages and minimize the impact on patients.

The minimum requirements for the SMPs include procedures for dealing with shortages, from identification to resolution. These procedures should include measures to reduce the shortage's impact, notification to regulatory authorities, and follow-up actions. MAHs should define roles, responsibilities, escalation processes and maintain records of root causes and mitigation measures after resolving shortages.

SPPs and SMPs should be submitted to the competent authorities upon request.

Regulations link

For templates Click here

End Product Testing versus Process Validation

End product testing versus validation? This is a question that is frequently discussed in the GMP environment. The argument is that if the specification of the end product fits, which is even included in the marketing authorisation, then the process must also fit. Otherwise the product would not conform to the specification.

It's not just the FDA that sees things differently. But the FDA also addresses this issue directly in a Warning Letter.

The FDA criticised the fact that no process validation could be demonstrated for a product that was manufactured, released and distributed. Specifically, it was criticised that it could not be shown that the manufacturing process was controlled with regard to a constant yield with consistent quality.

The company's response is interesting. It suggested analysing the release data in terms of safety and efficacy and then showing a summary of the release data in terms of content and microbiological count.

This answer was not well received. It was criticised that the company could not demonstrate sufficient certainty that batches had sufficient strength, quality and purity. The lack of a stability monitoring plan and a plan for dealing with complaints was also criticised.

Following the FDA quotes from its Process Validation Guidance what validation means - starting with development, through the actual process validation (called PPQ in the USA) and the "stage of control" in phase three of a process validation cycle. Prior to market supply, process qualification studies are important for the FDA and subsequent monitoring of the process. As is often the case in FDA Warning Letters on the subject of process validation, the FDA Process Validation Guidance is also cited with a link.

Specifically, the FDA requires

• a complete list of all products that are still on the US market within the expiry
• a plan that provides an overview of the above-mentioned products, the responsibilities of the reserved samples and their storage. The stability programme and complaints received and how to deal with them. 
• a plan for dealing with products that have quality defects, including how customer get notified and recalls are handled.

Conclusion: The argument that the final product testing shows that the manufacturing process works is not accepted in this Warning Letter. Validation is mandatory.

Access Warning Letter here

Example for common cause variation in Stastical process control

Here are some real-world examples of common cause variation in Statistical Process Control (SPC):

- Minor fluctuations in raw material properties, such as the thickness or density of a material, leading to small variations in the final product dimensions[1][2][3]

- Slight changes in environmental conditions like temperature or humidity from day to day, causing small shifts in a chemical process's yield[1][3]

- Natural variation in operator technique or skill level, resulting in small differences in product quality characteristics between individual workers[1][3]

- Random variation in machine performance over time due to normal wear and tear, leading to gradual changes in a process output[1][2][3]

- Minor differences in measurement instruments or calibration, contributing to small variations in data collected during the process[1][3]

Common cause variation is the inherent, random variability that is always present in a stable process. It represents the normal "noise" of the system and cannot be traced back to a specific, assignable source. As long as this variation remains within the control limits on a control chart, it indicates the process is in a state of statistical control.[1][2][3]

Citations:

[1] Achieving Process Stability with Common Cause Variation - iSixSigma https://www.isixsigma.com/dictionary/common-cause-variation/

[2] How to Identify Causes of Variation in Statistical Process Control https://safetychain.com/blog/identifying-variation-statistical-process-control

[3] What is Common Cause Variation in Six Sigma? - SixSigma.us https://www.6sigma.us/cause-variation/what-is-common-cause-variation/

[4] Common and Special Causes in Statistical Process Control - LinkedIn https://www.linkedin.com/advice/0/what-some-common-tools-techniques-identifying

[5] Common Cause and Special Cause - MSI Six Sigma Training https://www.msicertified.com/common-cause-and-special-cause/

Special cause variation in Stastical Process Control

Let's consider a manufacturing scenario where Statistical Process Control (SPC) is used to monitor and improve the quality of a production process for a specific product, such as automobile brake pads. 

In this example, the critical quality characteristic of interest is the thickness of the brake pads, which must fall within a specified range to meet safety and performance requirements.

Here's how SPC can be applied to monitor and control the thickness of brake pads:

1. Data Collection: The manufacturing process involves producing brake pads of a certain thickness. Measurements of the thickness are taken periodically from samples of brake pads produced during the production run.

2. Control Chart Creation: A control chart is created to monitor the thickness of the brake pads over time. The control chart typically consists of a central line representing the process mean and upper and lower control limits based on process variability.

3. Data Analysis: As measurements are collected and plotted on the control chart, the process variability and trends are analyzed. Any points that fall outside the control limits or exhibit non-random patterns (such as trends, shifts, or cycles) are investigated as potential special causes of variation.

4. Process Adjustment: If special causes of variation are detected, corrective actions are taken to address the root cause of the issue. This could involve adjusting machine settings, changing materials or processes, or providing additional training to operators.

5. Continuous Monitoring and Improvement: The process is continuously monitored using SPC techniques to ensure that the thickness of the brake pads remains within the desired range. Regular data collection and analysis help to identify opportunities for process improvement and prevent quality issues from recurring.

By using Statistical Process Control in this example, the manufacturer can ensure that the thickness of brake pads meets quality standards consistently, leading to improved product performance, customer satisfaction, and cost savings through reduced rework and scrap.

give me real world example for special cause variation in Stastical process control

Here are some real-world examples of special cause variation in Statistical Process Control (SPC):

Few other examples 

- A machine breaks down unexpectedly, causing a spike in cycle time or defect rate[1][2][3]

- A shipment of raw materials is contaminated, leading to an increase in product failures[1][2][4] 

- A power outage shuts down production for several hours, disrupting the normal process[2][3]

- A new operator makes a mistake in a critical process step, resulting in off-spec product[1][3]

- An earthquake or severe weather event damages equipment and facilities[2][4]

Special causes are unexpected, non-routine events that are not part of the normal process variation. They are assignable to a specific cause and can be corrected by adjusting the process. When special causes occur, they will show up as points outside the control limits or non-random patterns on a control chart[1][4].

The key is to quickly identify the special cause, determine the root source, and implement corrective action to bring the process back into a state of statistical control[1][3]. Preventing special causes requires proactive measures like preventive maintenance, operator training, and supplier quality audits[3].

Citations:

[1] The Power of Special Cause Variation: Learning from Process Changes https://www.isixsigma.com/dictionary/special-cause-variation/

[2] Common Cause Variation Vs. Special Cause Variation - Simplilearn.com https://www.simplilearn.com/common-vs-special-cause-of-variance-article

[3] Common and Special Causes in Statistical Process Control - LinkedIn https://www.linkedin.com/advice/0/what-some-common-tools-techniques-identifying

[4] How to Identify Causes of Variation in Statistical Process Control https://safetychain.com/blog/identifying-variation-statistical-process-control

[5] Common cause and special cause (statistics) - Wikipedia https://en.wikipedia.org/wiki/Common_cause_and_special_cause_%28statistics%29

A Guide to Statistical Process Control (SPC)

In today's competitive business landscape, maintaining consistent quality is paramount for success. Statistical Process Control (SPC) is a powerful tool that enables organizations to monitor and improve processes, ensuring that products and services meet the highest standards. By harnessing the principles of SPC, businesses can reduce variability, enhance efficiency, and ultimately drive customer satisfaction.

What is Statistical Process Control (SPC)?

Statistical Process Control is a methodical approach to quality management that uses statistical tools to monitor and control processes. By collecting and analyzing data over time, SPC helps organizations understand process performance, detect variations, and make informed decisions to maintain quality standards.

Key Concepts of SPC:

1. Control Charts: Control charts are a fundamental tool in SPC that visually display process data over time. By plotting data points against control limits, organizations can identify trends, shifts, or patterns that indicate whether a process is in control or out of control.

2. Variation: SPC distinguishes between common cause variation (inherent to the process) and special cause variation (resulting from external factors). Understanding these variations is crucial for taking appropriate action to improve processes.

3. Process Capability: Process capability analysis assesses the ability of a process to meet specifications. By comparing process variation to specification limits, organizations can determine whether a process is capable of producing products or services within desired quality standards.

Benefits of Implementing SPC:

1. Improved Quality: SPC helps organizations identify and address issues proactively, leading to higher quality products and services.

2. Cost Reduction: By reducing waste, rework, and defects, SPC helps organizations optimize processes and lower production costs.

3. Enhanced Decision-Making: Data-driven insights provided by SPC enable informed decision-making and continuous improvement initiatives.

4. Customer Satisfaction: Consistent quality assurance through SPC results in products and services that meet or exceed customer expectations, fostering loyalty and retention.

In conclusion, Statistical Process Control is a valuable methodology for organizations looking to achieve operational excellence and deliver superior quality. By embracing SPC principles and tools, businesses can drive efficiency, reduce defects, and gain a competitive edge in today's market. Start mastering SPC today to unlock the full potential of your processes and elevate your quality standards.

Sun Pharma's Dadra unit gets USFDA warning letter

Sun Pharma's Dadra unit had received an Official Action Indicated (OAI) status from the USFDA on April 11 this year. This was after the regulator had inspected the facility between December 4 to December 15, 2023.

Sun Pharma's Dadra unit is involved in the production of oral solid dosage forms and in the manufacturing of the generic Revlimid, which has been a key driver of sales for many pharma companies including Dr. Reddy's, in recent times.

Warning Letter to Indian Sterile Manufacturer due to egregious GMP Deficiencies 17.06.2024

The nine-day FDA inspection of an Indian pharmaceutical manufacturer had already taken place in October 2023. Due to the numerous and, as the FDA itself writes, egregious GMP violations and the inadequate response to the list of deficiencies by the manufacturer, a Warning Letter has now been issued. 

Insanitary conditions

The FDA classifies the medicinal products manufactured by the Indian pharmaceutical manufacturer as contaminated because they were manufactured, packaged or stored under insanitary conditions. The FDA inspectors found the manufacturing facilities to be in a state of disrepair, inadequately cleaned and maintained. Among the findings mentioned were residues next to the HEPA filters in the ISO 5 area, several barefoot employees in an ISO 8 area and employees bringing materials into the ISO 7 area without the required protective clothing and gloves. Sterile filling takes place in a RABS, which was visibly dirty.

And even if these deficiencies would be enough, the FDA lists further critical GMP deficiencies in its Warning Letter.

Inadequate, aseptic working methods

The FDA describes deficiencies that were observed during the manufacture of sterile medicinal products: Employees used a cloth to wipe down parts of the filling line and conveyor belt in the ISO 5 areas. In addition, employees blocked the protective air flow by leaning over open product. Employees did not wear goggles and had exposed skin during line set-up and aseptic operations. In addition, the FDA criticised the lack of monitoring of aseptic behaviour and the effectiveness of employee training.

Deficiencies in the media fill

During the inspection, it was noted that the aseptic operations simulated during the media fill were not sufficiently representative of commercial aseptic manufacturing operations. As routine production staff do not record manual interventions in the batch documentation, the media fill programme lacks representative data to determine the number and duration of interventions to be simulated during the media fill. In addition, during the inspection, numerous procedures were performed during routine manufacturing that were not simulated in the media fill.

Inadequate smoke studies

The FDA also criticised the smoke studies conducted to show the flow in the aseptic processing areas. Several instances of turbulent airflow were noted in critical areas of the filling line, even directly above the filling line. In addition, the smoke study videos did not include the manual filling operations that simulate actual production. Also, not all parts of the line were assembled as used in routine production.

Deficiencies in environmental monitoring and data falsification

The FDA criticised the fact that the required number of samples for environmental and personnel monitoring were not collected in accordance with the manufacturer's procedures. Instead, interviews with employees and the management of the microbiology laboratory revealed that it is common practice to fabricate results for samples that were never taken. In addition, results were altered that would otherwise not fulfil the defined specifications. During the inspection, numerous limit violations were also found in environmental and personnel monitoring samples.

Ineffective quality system

According to the FDA, the manufacturer does not have an effective quality system in accordance with GMP. In addition to the lack of effective management oversight of its manufacturing and laboratory operations, the FDA found that the quality department was unable to exercise appropriate authority or had inadequately implemented its responsibilities. Company management should promptly and comprehensively evaluate the company's global manufacturing operations to ensure that systems, processes and products are in compliance with FDA requirements.

Delay in the recall of medicinal products

Due to the serious GMP violations and the associated patient risk, the FDA had already advised the manufacturer in a conference call on 25 October 2023 to recall medicinal products from the inspected facility. On 27 October, the FDA published its own announcement. Despite numerous attempts by the FDA to obtain a decision on a recall, the Indian manufacturer did not initiate the necessary recall until 15 November 2023, i.e. approximately three weeks after the initial discussion.

Click here to get WL

CHMP confirms Suspension of Marketing Authorizations with Studies of Synapse Labs

The re-examination by the Committee for Medicinal Products for Human Use (CHMP) confirms the suspension of marketing authorizations with bioequivalence studies of Synapse Labs Pvt. Ltd.

In July 2023, critical inspection findings at Synapse Labs Pvt. Ltd, a contract research organization (CRO) in India, led the EMA to initiate an Article 31 referral procedure to assess the impact on the benefits and risks of medicinal products authorized on the basis of studies conducted at the CRO. After reviewing all information for the over 400 medicinal products tested by Synapse Labs Pvt. on behalf of EU companies, the CHMP has recommended the suspension for numerous generic marketing authorizations. For some marketing authorizations, sufficient data are available to demonstrate bioequivalence. For all other medicinal products, no or insufficient data were available to demonstrate bioequivalence. National authorities can defer the suspension of medicinal products of critical importance for a maximum of two years and companies must submit the required bioequivalence data for these medicinal products within one year. Applicants and marketing authorization holders have requested the CHMP to re-examine its opinion. In March 2024, the CHMP confirmed and adopted its final opinion.

This confirmation concludes the re-examination for some of the medicinal products concerned. The opinion will now be forwarded to the European Commission, which will take a final decision that is legally binding in all EU Member States.