An experimental vaccine prevented women from becoming persistently infected with a virus that is associated with half of all cervical cancers, researchers reported in the November 21, 2002, issue of the New England Journal of Medicine (http://www.ncbi.nlm.nih.gov/pubmed/12444178?dopt=Abstract ).
Human papilloma viruses (HPV) are extremely common sexually transmitted infections. In more than 90 percent of cases, the infections are harmless and go away without treatment.
However, certain types of HPV increase women’s risk for cancer of the cervix (the neck of the womb). HPV-16, the virus type that was the focus of the current study, is found in 50 percent of cervical cancers. About a dozen other HPV types are involved in most other cases of the disease.
Rare instance
Although the vast majority of HPV infections do not progress to cervical cancer, the rare instance when HPV infection persists seems to be important to the development of the disease.
“If a woman tests positive for HPV once, that does not mean she is likely to get cervical cancer,” says Allan Hildesheim, Ph.D., a senior investigator in the Division of Cancer Epidemiology and Genetics at the National Cancer Institute (NCI). “If she tests positive repeatedly over a period of years, that is more worrisome.”
The current study, he says, “is an exciting first step toward a vaccine that can prevent cervical cancer.” However, larger studies are needed to confirm that the vaccine is safe and effective for healthy young women, he adds.
Three shots
The study involved 2,392 women from 16 to 23 years in age. Participants were randomly assigned to receive three shots of either an HPV-16 vaccine or a placebo (a dummy substance). The study was double-blinded -- that is, neither the investigators nor the study participants knew who got the vaccine and who got the placebo. Participants were followed for an average of 17 months after getting the third shot.
Some women had HPV-16 infections or other cervical abnormalities when they enrolled in the study; others developed the infection before they received all three shots. These women (859 enrollees) were excluded when the researchers calculated the vaccine’s effectiveness.
Of the remaining 1,533 women, 41 developed HPV-16 infection -- all of these women were in the placebo group. Nine of the 41 women with HPV-16 infection went on to develop precancerous lesions (areas of abnormal tissue that may become cancerous). Twenty-two other women from the placebo group also developed precancerous lesions on their cervixes, but these were not associated with HPV-16.
By comparison, no one who got all three vaccine shots developed an HPV-16 infection. Twenty-two women receiving the vaccine did develop cervical abnormalities that can lead to cancer but these precancerous lesions were not associated with HPV-16.
Limitations
The vaccine tested in this study has several limitations, noted NCI’s Hildesheim. For one thing, the vaccine offers no protection against other types of HPV that can also cause cervical cancer. In addition, it’s unknown whether the vaccine’s protection against HPV-16 is long-lasting. Finally, it does not prevent HPV-16 infections already present at the time of vaccination from progressing to cancer.
The study, which was supported by Merck Research Laboratories, will continue until all the participants have been followed for four years. Laura A. Koutsky, Ph.D., of the University of Washington in Seattle, led the team of researchers who conducted this study. An editorial by Christopher P. Crum, M.D., of Brigham and Women's Hospital in Boston accompanies the report. There are other efforts to develop a cervical cancer vaccine, as well, including one trial sponsored by NCI that is not yet open to enrollment.
Pap Tests Still Needed
Most cervical cancers develop slowly through a series of abnormal changes in the cells of the cervix, changes most often related to an HPV virus. Regular Pap tests can detect these changes and the abnormal tissue can be removed. Pap tests would still be needed even if the experimental vaccine used in this study proves widely effective because the vaccine only works against one kind of HPV.
Pap tests are not 100 percent accurate, however, and many women do not have the tests regularly. In one national health survey, a fifth of women aged 18 to 64 had not had a Pap test in the past three years. A vaccine that prevented the HPV infections known to be behind most cervical cancers would be a powerful addition to disease prevention strategies.
Worldwide, about 500,000 new cases of cervical cancer are diagnosed each year, resulting in 250,000 deaths. The disease is the second or third most common cancer among women (cervical cancer and colorectal cancer are virtually tied for second place after breast cancer).
Thursday, April 16, 2009
Bioequivalence: What’s the hype about it?
What is Bioequivalence?
Bioequivalence (BE) studies are in vivo (in human) methods designed to compare the bioavailability (amount absorbed into the body blood circulation) of a medicinal product to an innovator or appropriate reference product when studied under similar experimental conditions.
Bioequivalence studies are additional tests performed on a particular medicine besides its routine in vitro (laboratory) tests.
In Malaysia, bioequivalence studies are required only for certain groups of medicine. The list is reviewed periodically to include more compounds. Regulatory authorities from other ASEAN countries will like to follow Malaysia in this requirement. After receiving advice from WHO, the regulators are working towards harmonization.
Why is Bioequivalence important?
Looking back at a black moment in history, the case of digoxin – a cardiac glycoside used in the treatment of heart failures. Digoxin, a modern medicine derived from the plant Digitalis purpura, has been introduced a century ago. Patients who switched between brands of digoxin had sudden episodes of uncontrolled heart failure while others experienced toxic side effects. Phenytoin, a medicine used in the treatment of epilepsy, is another example. While some had sudden uncontrolled episodes of epilepsy, others experienced toxic effects. These incidences sparked the US FDA to introduce tighter controls over the pharmaceutical manufacturing process, leading to the introduction of bioequivalence tests. A direct demonstration of the efficacy of a generic medicine would require a full-scale clinical trial in which their efficacy
could be compared. These clinical trials are very expensive and are normally undertaken by the innovator. In bioequivalence trials, one attempts to circumvent this direct approach by conducting a blood-level trial in which it is demonstrated that the generics give rise to essentially equivalent blood-level profiles in human volunteers. The principle underlying this concept is
important, namely that a generic medicine that results in essentially equivalent (compared with the innovator) blood-level profiles over time should elicit equivalent efficacy and safety.
“I normally buy medicine recommended by my friends”
“I have always obtained my medication from my family doctor / pharmacist”
How are Bioequivalence studies relevant to me?
Imagine a scenario whereby you are traveling to another town or country and you run out of your regular medicine. A simple solution would be to stop by a pharmacy or a local clinic to get your medication. However what happens when the pharmacy or clinic does not have the same brand of medicine you were taking? Of course, you can always opt for another brand –
maybe a generic. But let’s be reminded by the cases of digoxin and phenytoin. Ideally, the generic substitute must have exactly the same effect and safety profile as the brand you have been taking!
Take for example a medicine for treating high blood pressure (Tenormin® from AstraZeneca which contains atenolol). When you swallow the tablet, it reaches your stomach where it mixes with your stomach juices. The tablet will start to disintegrate (break) and dissolve. The mixture then slowly moves into your small intestine where it is absorbed into your blood stream.
Your blood vessels work as a network to distribute the medicine to the target location, e.g. your heart, where it will act to reduce blood pressure. After that, the medicine may first be converted into another form through a process called metabolism. Finally, the medicine is removed or eliminated from your body either through urine or faeces.
A bioequivalent generic substitute will have that the same amount atenolol absorbed at the same rate and extent when compared with Tenormin® at an acceptable range clinically. This will ensure proper blood pressure control. However, for a bio-inequivalent generic substitute, a different amount of atenolol is bioavailable and this may cause your blood pressure to be out-of-control!
A bioequivalent generic allows the Pharmacist or Doctor to switch brands confidently without any doubt of the efficacy and safety of that generic. Whether bioequivalence is just hype – it’s really up to you to decide. It’s worthwhile to know that in developed countries, healthcare professionals never dream of buying a product that is not bioequivalent!
Bioequivalence (BE) studies are in vivo (in human) methods designed to compare the bioavailability (amount absorbed into the body blood circulation) of a medicinal product to an innovator or appropriate reference product when studied under similar experimental conditions.
Bioequivalence studies are additional tests performed on a particular medicine besides its routine in vitro (laboratory) tests.
In Malaysia, bioequivalence studies are required only for certain groups of medicine. The list is reviewed periodically to include more compounds. Regulatory authorities from other ASEAN countries will like to follow Malaysia in this requirement. After receiving advice from WHO, the regulators are working towards harmonization.
Why is Bioequivalence important?
Looking back at a black moment in history, the case of digoxin – a cardiac glycoside used in the treatment of heart failures. Digoxin, a modern medicine derived from the plant Digitalis purpura, has been introduced a century ago. Patients who switched between brands of digoxin had sudden episodes of uncontrolled heart failure while others experienced toxic side effects. Phenytoin, a medicine used in the treatment of epilepsy, is another example. While some had sudden uncontrolled episodes of epilepsy, others experienced toxic effects. These incidences sparked the US FDA to introduce tighter controls over the pharmaceutical manufacturing process, leading to the introduction of bioequivalence tests. A direct demonstration of the efficacy of a generic medicine would require a full-scale clinical trial in which their efficacy
could be compared. These clinical trials are very expensive and are normally undertaken by the innovator. In bioequivalence trials, one attempts to circumvent this direct approach by conducting a blood-level trial in which it is demonstrated that the generics give rise to essentially equivalent blood-level profiles in human volunteers. The principle underlying this concept is
important, namely that a generic medicine that results in essentially equivalent (compared with the innovator) blood-level profiles over time should elicit equivalent efficacy and safety.
“I normally buy medicine recommended by my friends”
“I have always obtained my medication from my family doctor / pharmacist”
How are Bioequivalence studies relevant to me?
Imagine a scenario whereby you are traveling to another town or country and you run out of your regular medicine. A simple solution would be to stop by a pharmacy or a local clinic to get your medication. However what happens when the pharmacy or clinic does not have the same brand of medicine you were taking? Of course, you can always opt for another brand –
maybe a generic. But let’s be reminded by the cases of digoxin and phenytoin. Ideally, the generic substitute must have exactly the same effect and safety profile as the brand you have been taking!
Take for example a medicine for treating high blood pressure (Tenormin® from AstraZeneca which contains atenolol). When you swallow the tablet, it reaches your stomach where it mixes with your stomach juices. The tablet will start to disintegrate (break) and dissolve. The mixture then slowly moves into your small intestine where it is absorbed into your blood stream.
Your blood vessels work as a network to distribute the medicine to the target location, e.g. your heart, where it will act to reduce blood pressure. After that, the medicine may first be converted into another form through a process called metabolism. Finally, the medicine is removed or eliminated from your body either through urine or faeces.
A bioequivalent generic substitute will have that the same amount atenolol absorbed at the same rate and extent when compared with Tenormin® at an acceptable range clinically. This will ensure proper blood pressure control. However, for a bio-inequivalent generic substitute, a different amount of atenolol is bioavailable and this may cause your blood pressure to be out-of-control!
A bioequivalent generic allows the Pharmacist or Doctor to switch brands confidently without any doubt of the efficacy and safety of that generic. Whether bioequivalence is just hype – it’s really up to you to decide. It’s worthwhile to know that in developed countries, healthcare professionals never dream of buying a product that is not bioequivalent!
Generic Medicine: is it really a copy cat?
When it comes to healthcare we do not want to take risks. We want only the best for our families and ourselves. We may not have considered using a generic medicine because we may be concerned that it is just a copy cat. But how does this copy cat compare to its original brand?
What is Generic Medicine?
All medicines have two names:
Generic name
Brand name
The generic name refers to the active ingredient of the medicine. The manufacturer chooses a brand name that can be recognized, pronounced and remembered by everyone. For example, Zocor® is Merck Sharp & Dohme’s brand name for simvastatin, a generic name.
When a medicine is first developed, it is patented and sold exclusively under a single brand name. This is known as the innovator product. After the patent period expires, generic manufacturers may legally ‘copy’ the same active ingredient and give it a different
brand name. Generic medicines are made to be interchangeable with the innovator product. It contains the same active ingredient but usually contain different amounts of inactive ingredients known as excipients. Occasionally it differs from the innovator product in size, shape or colour. For instance, in Malaysia and Singapore, there are at least 8 brands (generics) competing with the innovator painkiller Voltaren®, all of which contain diclofenac sodium.
Why are Generic Medicines cheaper?
An innovator drug company spends a large sum of money (about US $500 to $600 million) on research and development of a new medicine, performing tests in the laboratory, on animals and humans, and obtaining approval for the medicine to be marketed. The high costs involved explain the high pricing aimed at reaping profits on the initial investment. Conversely, a generic manufacturer need not incur these costs. Therefore, a generic medicine is generally 30 to 60% cheaper than its innovator counterpart.
What about the quality of Generic Medicines?
To be assured of good quality medicine, it is important to check that it is registered with the regulatory authority. The Malaysian Drug Control Authority (DCA) gives registration numbers with MAL followed by 8 numerical digits. Singapore’s Health Science Authority (HSA) registers products with the code SIN followed by 5 numerical digits. DCA and HSA register only products
manufactured under Good Manufacturing Practice (GMP) environment. Periodic audits are performed on these companies to ensure strict compliance to the highest quality.
In vitro (laboratory) tests are performed according to international standards such as the British Pharmacopoeia (BP) and United States Pharmacopoeia (USP). The in vitro tests will show if a particular generic medicine:
• contains the correct amount of active ingredient
• contains excessive impurities and other related substances
• is uniform in size, shape and weight
• has appropriate hardness
• is not friable
• disintegrates and dissolves within a stipulated time frame
• is stable until its expiry date
However, some of us may have experiences whereby only the innovator brand works, not the generic brand. This could be because of our own bias towards generics or the generic is truly of inferior quality compared to the innovator; a condition known as nonbioequivalence.
So many brands – spoilt for choices!
Faced with so many brands for a particular medicine, a simple step is to ask your Pharmacist or Doctor for a professional opinion.
We should constantly exercise our consumer rights to know what we are buying or receiving. We can ask, “Is the product registered?”
If it is a generic, “Is it bioequivalent to the innovator?”
Take responsibility for you and your family’s health. Be an active partner with your healthcare professional in managing your medication needs. The first step in taking responsibility is to raise awareness and increase knowledge – so, congratulations for taking that first step – by reading this article!
What is Generic Medicine?
All medicines have two names:
Generic name
Brand name
The generic name refers to the active ingredient of the medicine. The manufacturer chooses a brand name that can be recognized, pronounced and remembered by everyone. For example, Zocor® is Merck Sharp & Dohme’s brand name for simvastatin, a generic name.
When a medicine is first developed, it is patented and sold exclusively under a single brand name. This is known as the innovator product. After the patent period expires, generic manufacturers may legally ‘copy’ the same active ingredient and give it a different
brand name. Generic medicines are made to be interchangeable with the innovator product. It contains the same active ingredient but usually contain different amounts of inactive ingredients known as excipients. Occasionally it differs from the innovator product in size, shape or colour. For instance, in Malaysia and Singapore, there are at least 8 brands (generics) competing with the innovator painkiller Voltaren®, all of which contain diclofenac sodium.
Why are Generic Medicines cheaper?
An innovator drug company spends a large sum of money (about US $500 to $600 million) on research and development of a new medicine, performing tests in the laboratory, on animals and humans, and obtaining approval for the medicine to be marketed. The high costs involved explain the high pricing aimed at reaping profits on the initial investment. Conversely, a generic manufacturer need not incur these costs. Therefore, a generic medicine is generally 30 to 60% cheaper than its innovator counterpart.
What about the quality of Generic Medicines?
To be assured of good quality medicine, it is important to check that it is registered with the regulatory authority. The Malaysian Drug Control Authority (DCA) gives registration numbers with MAL followed by 8 numerical digits. Singapore’s Health Science Authority (HSA) registers products with the code SIN followed by 5 numerical digits. DCA and HSA register only products
manufactured under Good Manufacturing Practice (GMP) environment. Periodic audits are performed on these companies to ensure strict compliance to the highest quality.
In vitro (laboratory) tests are performed according to international standards such as the British Pharmacopoeia (BP) and United States Pharmacopoeia (USP). The in vitro tests will show if a particular generic medicine:
• contains the correct amount of active ingredient
• contains excessive impurities and other related substances
• is uniform in size, shape and weight
• has appropriate hardness
• is not friable
• disintegrates and dissolves within a stipulated time frame
• is stable until its expiry date
However, some of us may have experiences whereby only the innovator brand works, not the generic brand. This could be because of our own bias towards generics or the generic is truly of inferior quality compared to the innovator; a condition known as nonbioequivalence.
So many brands – spoilt for choices!
Faced with so many brands for a particular medicine, a simple step is to ask your Pharmacist or Doctor for a professional opinion.
We should constantly exercise our consumer rights to know what we are buying or receiving. We can ask, “Is the product registered?”
If it is a generic, “Is it bioequivalent to the innovator?”
Take responsibility for you and your family’s health. Be an active partner with your healthcare professional in managing your medication needs. The first step in taking responsibility is to raise awareness and increase knowledge – so, congratulations for taking that first step – by reading this article!
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