Generic HGH, be cautious of potential problems

Cautions and Potential Problems with
Generic and Compounded HGH, (Human Growth Hormone, generically called somatropin)

by Elmer M. Cranton, M.D.

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Advances in biotechnology have made it possible to produce recombinant human growth hormone (rHGH) with full HGH activity. It is very time consuming and expensive, however, to achieve complete safety after it is has been extracted, purified and packaged.

If a less expensive, compounded, or generic HGH product is considered for personal use, it is imperative that you first insure that that the ingredients meet required standards for registration with the FDA. "Somatropin" is merely a generic name for HGH. FDA registered HGH products, including bulk products used in compounding, are assigned an official NDC number (National Drug Code). Without that code, it is difficult or impossible to know if a product is pure and unadulterated. Unfortunately, the FDA has blocked compounding pharmacies from packaging HGH, even with FDA approved bulk ingredients.

HGH is large, a complex protein made in a cell culture using biotechnology—a process that is enormously more complex and different from manufacture of other types of generic drugs such as diuretics and blood pressure medicines. HGH is produced with delicate biological cultures using living cells replicating in complex mixtures of cell nutrients. It is difficult to ensure that any two protein cultures will produce identical molecules with the same 3-dimensional configuration in final product.

Purification and handling of proteins produced in cell cultures can cause variations in folding, unfolding, cross-linkages, and variable aggregates of multiple proteins hooked together as dimers and polymers. These can cause immune responses and allergy to HGH, even endogenously produced HGH by the pituitary gland. Extraction and purification are very complex and expensive. Tiny residues from the cell culture can contaminate the end-product. It is relatively easy to get hormone activity, but extensive testing and quality control is required to insure safety for any new follow-on protein biological (FOPP) such as generic HGH.

To be completely safe, dimers, polymers, aggregates, improper folding, glycosylation, broken cross-linkages, pyrogens, and contaminants must be strictly limited during manufacture and packaging. The HGH molecule is fragile. Freeze drying and other steps in the packaging process can alter its structure. Such abnormalities may not block hormone activity, and the end product may seem to work quite well, but the altered molecules may stimulate immune reactions and cause allergy and desensitization to HGH over time, with subsequent and permanent loss of hormone response in the body. Such autoimmunity has been reported from injected HGH in an altered form, causing the body to neutralize internally produced as well as injected HGH. Adverse reactions may also include rashes and anaphylactic shock.

To insure purity and safety, I recommend that you use only FDA approved HGH with an FDA NDC license number (National Drug Code). Buy only from a trusted source, as there are a number of counterfeit products being marketed with false labeling that look exactly like trusted brands.

Because the FDA will not allow compounding pharmacists to package HGH, even using approved bulk ingredients, reliable sources remain with major pharmaceutical companies.

A new HGH product, Onmitrope™, first became available in 2007 at a somewhat lower cost than other major brand name products. Onmitrope™ is manufactured by Sandoz Pharmaceutical Company has been recently approved by the FDA.

If do not load the syringes yourself, and if your HGH comes in pre-loaded syringes, we recommend that you insist on assurance that the ingredients are not counterfeit and that the syringes contain an FDA approved product with an NDC code. Each vial comes with an FDA approved package insert. Some clinics dispense the less expensive types of HGH without that FDA registration code, and provide products for their patients that have not undergone all of the necessary quality control procedures required for safe use. Patient safety should be the foremost consideration.

Products manufactured in FDA registered facilities have been tested to assure safety. Some generic and products from foreign sources now being marketed, often at much lower prices, have not been tested for complete safety and purity.

Recombinant human growth hormone is manufactured in cell cultures and is a very large protein with a molecular weight greater than 22,000. It is composed of more than 190 amino acids linked together in a very precise order, then folded and cross linked at strictly defined locations. The result is growth hormone activity identical to that produced in the human pituitary gland. The 3-dimensional shape must be exact for proper effect—much like a key that must be in exactly the right shape to open a lock. Molecular variations in HGH may have hormone effect but can stimulate rejection by the immune system.

The reason HGH is so expensive is because of the expensive quality control and testing required to prove safety, and the great care required for proper extraction, purification and packaging. Improper handling or agitation of the HGH molecule during manufacture, separation, purification, freeze drying and packaging can lead to potentially dangerous side effects over a period of time when injected.

It is recommended to use only products with an FDA assigned NDC code be considered for use and that they be obtained from a trusted source.

Counterfeits with unknown ingredients have appeared in the marketplace, with identical packaging including even the manufacturer’s hologram. One such product was shown to contain only chorionic gonadotropin.

REFERENCES

Dudzinski. Issues Relevant to Generic Biologics via § 505(b)(2) or Abbreviated Pathways. Harvard School of Law. (Click this link to read the full text)

W.V. Moore and P. Leppert, 1980. Role of Aggregated Human Growth Hormone (hGH) in Development of Antibodies to hGH. Journal of Clinical Endocrinology and Metabolism 51:691-697.

Dannies PS.. Protein Folding and Deficiencies Caused by Dominant-Negative Mutants of Hormones. Vitamins and Hormones. 2000;58:l-26.