Marinduque Mainland from Tres Reyes Islands

Marinduque Mainland from Tres Reyes Islands
View of Marinduque Mainland from Tres Reyes Islands-Click on photo to link to Chateau Du Mer

WELCOME TO MY SITE AND HAVE A GOOD DAY

If this is your first time in this site, welcome. It has been my dream that my province, Marinduque, Philippines becomes a world tourist destination not only during Easter Week but also whole year round. You can help me achieve my dream by telling your friends about this site. The photo above is your own private beach at The Chateau Du Mer Beach Resort. The sand is not as white as Boracay, but it is only a few steps from your front yard and away from the mayhem and crowds of Boracay. I have posted some of my favorite Filipino and American dishes and recipes on this site also. Some of the photos and videos on this site, I do not own. However, I have no intention on infringement of your copyrights. Cheers!

Tuesday, April 23, 2019

Some Photos from a Recent Wedding at Chateau Du Mer

Photo by Rosette Pitero Sotta

On April 6, 2019, a wedding ceremony and reception was held at the Chateau Du Mer Conference Hall and Beach House. The following are some of the photographs taken by 6PM Photography Studio. Ms Rosette Pitero Sotta was the caterer of this memorable event in the life of Amiel and Ericka. Congratulations to the newly weds from the owners (Dave and Macrine Katague) of the Chateau Du Mer Beach House and Conference Hall.

The bride on the Bridge of Love -focal point in the landscaping design of the Beach House


https://www.facebook.com/sixpmstudio/videos/2359939200961414/

Saturday, April 20, 2019

Chemistry, Manufacturing and Control Requirements for New Drug Application(NDA)



In my previous posting, I discussed the general overview of new drug development in the US and FDA's role in the process. In this article I am focusing on the Chemistry portion of a New Drug Application (NDA) which was my expertise when I was still working for FDA. I worked for FDA from September, 1990 up to October, 2002. Twelve productive years of my professional career.

I am listing below a table of all Chemistry, Manufacturing and Control(CMC) guidance both in draft and final form. As a former Chemistry team leader in one of the divisions in the Center of New Drugs, I have some input on the contents of a few of these guidance. These guidance are available in the Internet for everyone.

Below is a table of Chemistry, Manufacturing and Controls (CMC) Guidance showing,
category, title status( draft or final) and date.

1. Chemistry, Manufacturing, and Controls (CMC) Analytical Procedures and Methods Validation (PDF - 91KB)1 Draft Guidance 08/30/00

2. Chemistry, Manufacturing, and Controls (CMC) Assay Development for Immunogenicity Testing of Therapeutic Proteins (PDF - 161KB)2 Draft Guidance 12/04/09

3. Chemistry, Manufacturing, and Controls (CMC) Botanical Drug Products (PDF - 437KB)3 Final Guidance 06/01/04
Taken at My Retirement Party-FDA Colleagues-2002

4. Chemistry, Manufacturing, and Controls (CMC) Changes to an Approved Application for Specified Biotechnology and Specified Synthetic Biological Products (PDF - 33KB)4 Final Guidance 07/01/97

5. Chemistry, Manufacturing, and Controls (CMC) Changes to an Approved NDA or ANDA (PDF - 108KB)5 Final Guidance 04/01/04

6. Chemistry, Manufacturing, and Controls (CMC) Changes to an Approved NDA or ANDA: Questions and Answers (PDF - 35KB)6 Final Guidance 01/01/01

7. Chemistry, Manufacturing, and Controls (CMC) Changes to an Approved NDA or ANDA; Specifications – Use of Enforcement Discretion for Compendial Changes (PDF - 18KB)7 Final Guidance 11/19/04

8. Chemistry, Manufacturing, and Controls (CMC) CMC Postapproval Manufacturing Changes Reportable in Annual Reports (PDF - 78KB)8 Draft Guidance 06/24/10

9. Chemistry, Manufacturing, and Controls (CMC) Comparability Protocols -- Chemistry, Manufacturing, and Controls Information (PDF - 240KB)9 Draft Guidance 02/25/03

10. Chemistry, Manufacturing, and Controls (CMC) Container Closure Systems for Packaging Human Drugs and Biologics (PDF - 164KB)10 Final Guidance 05/01/99

11.Chemistry, Manufacturing, and Controls (CMC) Container Closure Systems for
Packaging Human Drugs and Biologics -- Questions and Answers (PDF - 15KB)11 Final Guidance 05/01/02

12. Chemistry, Manufacturing, and Controls (CMC) Demonstration of Comparability of Human Biological Products, Including Therapeutic Biotechnology-derived Products12 Final Guidance 04/01/96

13, Chemistry, Manufacturing, and Controls (CMC) Development of New Stereoisomeric Drugs13 Final Guidance 05/01/92

14. Chemistry, Manufacturing and Controls (CMC) Drug Master Files (DMFs)14 Additional Information regarding DMF's

Letter of Appreciation from the CEO and President of Bristol Myers-Sion Boney,1997

15. Chemistry, Manufacturing, and Controls (CMC) Drug Master Files for Bulk Antibiotic Drug Substances (PDF - 23KB)15 Final Guidance 11/01/99

16. Chemistry, Manufacturing, and Controls (CMC) Drugs, Biologics, and Medical Devices Derived from Bioengineered Plants for Use in Humans and Animals (PDF - 88KB) Draft Guidance 09/11/02

17. Chemistry, Manufacturing, and Controls (CMC) Environmental Assessment of Human Drug and Biologics Applications (PDF - 188KB)17 Final Guidance 07/01/98

18. Chemistry, Manufacturing, and Controls (CMC) Format and Content for the CMC Section of an Annual Report (PDF - 29KB)18 Final Guidance 09/01/94

19. Chemistry, Manufacturing, and Controls (CMC) Incorporation of Physical-Chemical Identifiers into Solid Oral Dosage Form Drug Products for Anticounterfeiting (PDF - 79KB)19 Draft Guidance 07/14/09

20. Chemistry, Manufacturing, and Controls (CMC) INDs for Phase 2 and Phase 3 Studies Chemistry, Manufacturing, and Controls Information (PDF - 193KB)20 Final Guidance 05/20/03

21. Chemistry, Manufacturing, and Controls (CMC) IND Meetings for Human Drugs and Biologics Chemistry, Manufacturing, and Controls Information (PDF - 30KB)21 Final Guidance 05/01/01

Ceremony during my Equal Employment Opportunity Award(EE0)

22. Guidance for Industry: Interpreting Sameness of Monoclonal Antibody Products Under the Orphan Drug Regulations (PDF - 26KB)22

23. Chemistry, Manufacturing, and Controls (CMC) Liposome Drug Products: Chemistry, Manufacturing, and Controls; Human Pharmacokinetics and Bioavailability; and Labeling Documentation (PDF - 45KB)23 Draft Guidance 08/21/02

24. Chemistry, Manufacturing, and Controls (CMC) Monoclonal Antibodies Used as Reagents in Drug Manufacturing (PDF - 29KB)24 Final Guidance 03/01/01

25. Chemistry, Manufacturing, and Controls (CMC) Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Drug Products (PDF - 361KB)25 Draft Guidance 11/19/98

26. Chemistry, Manufacturing, and Controls (CMC) Nasal Spray and Inhalation Solution, Suspension, and Drug Products (PDF - 116KB)26 Final Guidance 07/01/02

27. Chemistry, Manufacturing, and Controls (CMC) NDAs: Impurities in Drug Substances (PDF - 11KB)27 Final Guidance 02/01/00

28. Chemistry, Manufacturing, and Controls (CMC) Orally Disintegrating Tablets (PDF - 52KB)28 Final Guidance 12/17/08

29. Chemistry, Manufacturing, and Controls (CMC) PAC-ATLS: Postapproval Changes - Analytical Testing Laboratory Sites (PDF - 76KB)29 Final Guidance 04/28/98

Some of My FDA Awards

30. Chemistry, Manufacturing, and Controls (CMC) Residual Drug in Transdermal and Related Drug Delivery Systems (PDF - 44KB)30 Draft Guidance 08/02/10

31. Chemistry, Manufacturing, and Controls (CMC) Residual Solvents in Drug Products Marketed in the United States (PDF - 52KB)31 Final Guidance 11/24/09

32. Chemistry, Manufacturing, and Controls (CMC) Reviewer Guidance, Validation of Chromatographic Methods (PDF - 703KB)32 Final Guidance 11/01/94

33. Chemistry, Manufacturing, and Controls (CMC) Size of Beads in Drug Products Labeled for Sprinkle (PDF - 43KB)33 Draft Guidance 01/18/11

34. Chemistry, Manufacturing, and Controls (CMC) Submitting Documentation for the Manufacturing of and Controls for Drug Products (PDF - 1048KB)34 Final Guidance 02/01/87

35. Chemistry, Manufacturing, and Controls (CMC) Guidelines for Submitting Samples and Analytical Data for Methods Validation Final Guidance 02/01/87

36. Chemistry, Manufacturing, and Controls (CMC) Submitting Supporting Documentation in Drug Applications for the Manufacture of Drug Substances (PDF - 94KB)36 Final Guidance 02/01/87

37. Chemistry, Manufacturing, and Controls (CMC) SUPAC-IR: Immediate-Release Solid Oral Dosage Forms: Scale-Up and Post-Approval Changes: Chemistry, Manufacturing and Controls, In Vitro Dissolution Testing, and In Vivo Bioequivalence Documentation (PDF - 60KB)37 Final Guidance 11/01/95

38. Chemistry, Manufacturing, and Controls (CMC) SUPAC-IR Questions and Answers about SUPAC-IR Guidance38 Final Guidance 02/18/97

39. Chemistry, Manufacturing, and Controls (CMC) SUPAC-IR/MR: Immediate Release and Modified Release Solid Oral Dosage Forms Manufacturing Equipment Addendum (PDF - 117KB)39 Final Guidance 01/01/99

40. Chemistry, Manufacturing, and Controls (CMC) SUPAC-MR: Modified Release Solid Oral Dosage Forms Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls; In Vitro Dissolution Testing and In Vivo Bioequivalence Documentation (PDF - 215KB)40 Final Guidance 10/06/97

41. Chemistry, Manufacturing, and Controls (CMC) SUPAC-SS: Nonsterile Semisolid Dosage Forms Manufacturing Equipment Addendum (PDF - 61KB)41 Draft Guidance 12/01/98

42. Chemistry, Manufacturing, and Controls (CMC) SUPAC-SS: Nonsterile Semisolid Dosage Forms; Scale-Up and Post-Approval Changes: Chemistry, Manufacturing and Controls; In Vitro Release Testing and In Vivo Bioequivalence Documentation (PDF - 118KB)42 Final Guidance 05/01/97

43. Guidance for Industry - The Sourcing and Processing of Gelatin to Reduce the Potential Risk Posed by Bovine Spongiform Encephalopathy (BSE) in FDA-Regulated Products for Human Use The Sourcing and Processing of Gelatin to Reduce the Potential Risk Posed by Bovine Spongiform Encephalopathy (BSE) in FDA-Regulated Products for Human Use 09/01/97

My election to the United States Pharmacopeia Council of Experts is one of the highlight of my career with FDA

As a Chemistry Team Leader, you need to be familiar with contents of these 43 guidances, so when representatives from the Pharmaceutical firms ask you a question, you should be able to refer them to the guidance. If you can answer their question without referring to the guidance, the firm's representative look at you with high regard and respect. It is therefore imperative that you know most of the important requirements for an NDA submission as well as the post NDA requirements in the manufacture, chemistry and controls of an IND or NDA. A Guidance is not a Federal Regulation/Law. 21CFR (Code of Federal Regulation), gives FDA mandate to enforce drug and food laws in US. Source: www.fda.gov

My twelve years in FDA was the happiest and most productive years of my professional life. Macrine and my involvement with the Filipino-American community in the tristate area will also be memories that we will never forget.

Thursday, April 18, 2019

Development of New Drugs in the United States

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Image from medscape.com

As a retired FDA employee involved in the development of new drugs in the Division of Anti-Infective Drug Products, Office of New Drug Chemistry, Center for New Drugs for over twelve years, I had often been asked by several of my blog readers to write a summary and an overview of new drug development in the US.

I had been postponing it, because I thought the subject is confidential, but when I started browsing in the WEB I found several articles on the subject. I even found a Chemistry manufacturing supplement that I had approved several years ago. The letter of approval and the chemist review was printed in the Internet. However, the specifics of the supplement was erased in the approval letter as well as in the chemist review. The patent of the drug discussed had expired, so it is open to generic companies, otherwise the chemist review and letter of approval will never be made public. I am getting out of the subject, but let me start on the subject right now.
Two of my colleagues in FDA-1995

New Chemical Entity (NCE) development

Broadly the process can be divided into pre-clinical and clinical work.

Pre-clinical.

New Chemical Entities (NCEs)(also known as New Molecular Entities (NMEs)) are compounds which emerge from the process of drug discovery. These will have promising activity against a particular biological target thought to be important in disease; however, little will be known about the safety, toxicity, pharmacokinetics and metabolism of this NCE in humans. It is the function of drug development to assess all of these parameters prior to human clinical trials. A further major objective of drug development is to make a recommendation of the dose and schedule to be used the first time an NCE is used in a human clinical trial ("first-in-man" (FIM) or First Human Dose (FHD)).

In addition, drug development is required to establish the physicochemical properties of the NCE: its chemical makeup, stability, solubility. The process by which the chemical is made will be optimized so that from being made at the bench on a milligram scale by a synthetic chemist, it can be manufactured on the kilogram and then on the ton scale. It will be further examined for its suitability to be made into capsules, tablets, aeresol, intramuscular injectable, subcuteneous injectable, or intravenous formulations. Together these processes are known in preclinical development as Chemistry, Manufacturing and Control (CMC).

Note: The CMC portion of was my primary function as the Team Chemistry Leader during my employment with FDA

Many aspects of drug development are focused on satisfying the regulatory requirements of drug licensing authorities. These generally constitute a number of tests designed to determine the major toxicities of a novel compound prior to first use in man. It is a legal requirement that an assessment of major organ toxicity be performed (effects on the heart and lungs, brain, kidney, liver and digestive system), as well as effects on other parts of the body that might be affected by the drug (e.g. the skin if the new drug is to be delivered through the skin). While, increasingly, these tests can be made using in vitro methods (e.g. with isolated cells), many tests can only be made by using experimental animals, since it is only in an intact organism that the complex interplay of metabolism and drug exposure on toxicity can be examined.

The information gathered from this pre-clinical testing, as well as information on CMC, and is submitted to regulatory authorities (in the US, to the FDA), as an Investigational New Drug application or IND. If the IND is approved, development moves to the clinical phase.

Clinical phase.

Clinical trials involves three steps: Phase I trials, usually in healthy patients, determine safety and dosing Phase II trials are used to get an initial reading of efficacy and further explore safety in small numbers of sick patients Phase III trials a large, pivotal trials to determine safety and efficacy in sufficiently large numbers of patients

The process of drug development does not stop once an NCE begins human clinical trials. In addition to the tests required to move a novel drug into the clinic for the first time it is also important to ensure that long-term or chronic toxicities are determined, as well as effects on systems not previously monitored (fertility, reproduction, immune system, etc.). The compound will also be tested for its capability to cause cancer (carcinogenicity testing).

If a compound emerges from these tests with an acceptable toxicity and safety profile, and it can further be demonstrated to have the desired effect in clinical trials, then it can be submitted for marketing approval in the various countries where it will be sold. In the US, this process is called a New Drug Application or NDA. Most NCEs, however, fail during drug development, either because they have some unacceptable toxicity, or because they simply do not work in clinical trials.

As this drug discovery process becomes more expensive it is becoming important to look at new ways to bring forward NCEs. One approach to improve efficiency is to recognize that there are many steps requiring different levels of experimentation. The early phase of drug discovery actually has components of real innovation, components of experimentation and components that involve set routines. This model of Innovation, Experimentation, and Commoditization ensures that new ways to do work are adopted continually. This model also allows the discipline to use appropriate internal and external resources for the right work.

Cost

Studies published by diMasi et al in 2003 report an average pre-tax cost of approximately $800 million to bring a new drug (i.e. a drug with a new chemical entity) to market. A study published in 2006 estimates that costs vary from around $500 million to $2 billion depending on the therapy or the developing firm. A study published in 2010 in the journal Health Economics, including an author from the US Federal Trade Commission, was critical of the methods used by diMasi et al but came up with a higher estimate of ~$1.2B. Critic Marcia Angell, M.D., a former editor of the New England Journal of Medicine, has called that number grossly inflated, and estimates that the total is closer to $100 million. A 2011 study also critical of the diMasi methods, puts average costs at $55 million.

Success rate

Candidates for a new drug to treat a disease might theoretically include from 5,000 to 10,000 chemical compounds. On average about 250 of these will show sufficient promise for further evaluation using laboratory tests, mice and other test animals. Typically, about ten of these will qualify for tests on humans. A study conducted by the Tufts Center for the Study of Drug Development covering the 1980s and 1990s found that only 21.5 percent of drugs that start phase I trials are eventually approved for marketing. Now you know why the drugs you purchased in the pharmacy is very expensive ( except the generic drugs). Most Americans will not be able to afford new drugs if they do not have insurance.

The mission of FDA is to enforce laws enacted by the U.S. Congress and regulations established by the Agency to protect the consumer's health, safety, and pocketbook. The Federal Food, Drug, and Cosmetic Act20 is the basic food and drug law of the U.S. With numerous amendments it is the most extensive law of its kind in the world. The law is intended to assure consumers that foods are pure and wholesome, safe to eat, and produced under sanitary conditions; that drugs and devices are safe and effective for their intended uses; that cosmetics are safe and made from appropriate ingredients; and that all labeling and packaging is truthful, informative, and not deceptive.Code of Federal Regulations (CFR)

Code Of Federal Regulations (CFR)21. The final regulations published in the Federal Register22 (daily published record of proposed rules, final rules, meeting notices, etc.) are collected in the CFR. The CFR is divided into 50 titles that represent broad areas subject to Federal regulations. The FDA's portion of the CFR interprets the The Federal Food, Drug, and Cosmetic Act23 and related statutes. Section 21 of the CFR24 contains most regulations pertaining to food and drugs.

Note: I hope you found the above posting informative. My next posting on this subject will be on the Chemistry, Manufacturing and Control(CMC) Requirements for IND's and NDA's. If you find this posting either boring or interesting, let me know via comments. Thank You.

First Posting: 2011

Sunday, April 14, 2019

Pleasant Memories of My Gardens at Chateau Du Mer

The following photos I took from my gardens at Chateau Du Mer, Amoingon, Boac, Marinduque, Philippines in 2011.










I hope you enjoy the above pictures! I had fun taking them! Good Day to All!

Wednesday, April 10, 2019

Life is Short, So Enjoy it to the Fullest

It is spring time here in Northern California. It is time for some inspiration readings!


LIFE IS SHORT... ENJOY & LIVE LIFE TO THE FULLEST!!!
🔹Love God and others More!✔
🔹Take time to PRAY and Read the Word of God! ✔
🔹Drink Plenty of water. ✔
🔹EAT:
Breakfast like a KING,
Lunch like a Prince &
Dinner like a pauper. ✔
🔹Live with the 3 E's--
Energy,
Enthusiasm &
Empathy.✔
🔹Play good games.✔
🔹Read more books than you did in 2018.✔
🔹Sit in silence for at least 10 minutes each day.✔
🔹Sleep for 7 hours.✔
🔹Take a 10-30 minutes walk daily And while you walk...😊 Smile.✔
🔹Don't over do. Keep your limits.✔
🔹Don't take yourself so seriously. No one else does.✔
🔹Don't waste your precious energy on gossip.✔
🔹Dream more while you are awake.✔
🔹Envy is a waste of time. You already have all you need.✔
🔹Forget issues of the past. Don't remind your partner with his/her mistakes of the past. That will ruin your present Happiness.✔
🔹Life is too short to waste time hating anyone. Don't hate others.✔
🔹Make peace with your past so it won't spoil the present.✔
🔹No one is in charge of your happiness except you.✔
🔹Smile and Laugh More.✔
🔹You don't have to win every argument, Agree to disagree. ✔
🔹Call your family often.✔
🔹Each day give something good to others.✔
🔹Forgive everyone for everything.✔
🔹Spend time with people over the age of 70 & under the age of 6.✔
🔹Try to make at least three people smile each day.✔
🔹What other people think of you is none of your business.✔
🔹Do the right thing!✔
🔹GOD heals everything.✔
🔹However good or bad a situation is, it will change.✔
🔹No matter how you feel, Get up, Dress up and Show up. The best is yet to come.✔
🔹When awake in the morning Thank GOD for it.✔
🔹Your Inner most is always happy...
So, be Happy. ✔
ABOVE IS A REPOST
FROM:Jone Jingco Haimer
Building this beach house is one of our life's fullest enjoyment!

Thursday, April 4, 2019

Video Memories of Macrine's 80th Birthday

Last week, we celebrated Macrine's 83rd birthday with a very simple party. About 90% of the guests were also present when we celebrated her 80th birthday. A few of the guests were inquiring where is the videographer who took an excellent and unforgettable video now. I told them he is back in Australia. He is my nephew and namesake.

The video is one of the many pleasant memories of my nephew's visit three years ago. Three Years ago, Macrine could still swim and walk. Today she is wheel-chaired bound due a double hip surgery, that was not too successful.


The following video was taken by my nephew and Namesake from Australia three years ago.


My Auntie Macrine's 80th | "It's been a long time!" from Dave Katague on Vimeo.


For more videos of Dave Katague:https://www.youtube.com/watch?v=aFALi2TsbbI

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