L6 - Other good practices?

Question 1

Advantages of Nanomedicines

Answer 1

1. Effective in targeting difficult-to-reach sites (such as tumour sites
2. Improved solubility, bioavailability & reduced side effects
3. Achieve same therapeutic effect with smaller doses

Question 2

Name some examples of QbD/PATs?

Answer 2

NIR, Rama spectroscopy, X-ray diffraction

Question 3

List the advantages and benefits of QbD/PAT

Answer 3

1. Non destructive, unlike conventional QC
2. Deeper process understanding, better control and better quality assurance of entire batch
3. Real time release of products (instead of waiting to be released)
4. Reduced post-approval submissions to regulator
5. Cost-saving for industry

Question 4

List the challenges of QbD/PAT implementation

Answer 4

1. Requires deeper science and technological knowledge that personnel from regulations and industry may not be familiar with
2. High Financial investment in PAT due to high initial capital outlay
3. Companies’ old habits are difficult to change
4. Manufacturers feel that PAT may reveal inadequacies and are discouraged to use it
5. Regulators are not ready for QbD/PAT submissions as they are used to the old paradigm of QbT

Question 5

What are some of the limitations of QbT?

Answer 5

• Product/batch only tested at the end of the manufacturing process
• Can only test on a ‘representative sample size’
• Tests are destructive
• Can test only if the test method is specific, accurate and reliable
• Defects are only picked up at the end of the manufacturing process so defective products cannot be rectified/reworked
• QC tests not conducted and released in real-time, taking up expensive warehouse space

Question 6

What are disadvantages of traditional batch manufacturing of tablets?

Answer 6

• Intermediate products collected after each unit operation
• Finished product collected at end of batch manufacturing
• QC tests performed at off-line laboratories and finished products quarantined at warehouse
• Total batch processing takes weeks, resulting in increased costs

Question 7

Importance of inspecting API quality

Answer 7

• APIs responsible for therapeutic effect of drug product
• Without APIs, product is basically placebo
• Bulk of APIs produced in Asia

Question 8

What are pharmaceutical excipients?

Answer 8

Substances which are re-combined with active pharmaceutical ingredients to form finished product

Question 9

Name some examples of single use technology

Answer 9

• Single-use cell banking bags
• Pre-packed chromatic columns and buffers
• Single use syringes and injection ports
• 3D printed valves

Question 10

What are some things that are tested in SUTs?

Answer 10

• Material compatibility
• Extractables
• Biocompatibility
• Animal origins
• Particulate control
• Bioburden control
• Absorption

Question 11

What is the role of GMP/GDP in compliance and vigilance in supply chains?

Answer 11

1. Assure quality of API/products
2. Deter Manipulation by unscrupulous supply chain players
3. Detect Adulterated Products

Question 12

Name some benefits of ASEAN MRA on GMP inspection

Answer 12

1. Avoid duplication of GM audits
2. Save time, resources and cost
3. Facilitate trade across ASEAN borders
4. Quicker access to products by ASEAN patients
5. Harmonised inspection system to that of PIC/S
6. Increase attractiveness of ASEAN to investors from larger economies

Question 13

What is a register of LIS?

Answer 13

Listed Inspection service. Countries that are part of LIS can inspect for GMP/GDP

Question 14

As of now, what are the countries that are included in the ASEAN LIS?

Answer 14

Singapore, Malaysia, Indonesia, Thailand, Philippines

Question 15

What is the current scope of ASEAN Sectoral MRA?

Answer 15

Finished dosage forms ONLY

Question 16

What does ASEAN MRA on GMP inspection NOT include?

Answer 16

1. Manufacture of APIs

2. Manufacture of Biologicals

Question 17

What are some advantages of continuous manufacturing?

Answer 17

1. Integrated processes (hence fewer steps)
2. Shorter batch processing time
3. Smaller equipment and facilities (more flexible, reduce inventory, lower capital cost)
4. On-line monitoring and QC via PAT (Higher QA level, more consistent quality, RTR)
5. Overall cost reduction

Question 18

Why is GMP compliance and process control important at API manufacturing sites?

Answer 18

1. It can ensure the QUALITY of APIs (e.g. particle size)
2. It can ensure PURITY (e.g. enantiomers)
3. It can ensure API supply chain integrity

Question 19

What are some issues posed by having an increased number of players in API and product supply chains?

Answer 19

1. Potential points for interference of API/product

2. Falsified medicines

Question 20

Can excipients be regarded as inactive or inert ingredients?

Answer 20

No. Note that global supply chain can also affect the supply integrity of excipients

Question 21

One important property of a SUT

Answer 21

Materials that make up SUT must be inert

Question 22

What are some benefits of using SUTs?

Answer 22

1. Better cross-contamination control = higher QA level
2. “Flexible” manufacturing that requires less space = save time and cost
3. Allow SUT usage in other pharmaceutical and healthcare sectors such as hospital pharmacies

Question 23

Steps in guideline development:

Answer 23

1. Consensus building
2. ICH parties consensus on technical document
3. Regulatory consultation and discussion
4. Adaptation of ICH harmonised guideline
5. Implementation